Asthma is one of the most common chronic diseases in the United States, and its prevalence has been increasing since 1980. In 2000, asthma was responsible for 4,487 deaths, about 0.5 million hospitalizations, 1.8 million visits to the emergency room, and 10.4 million visits to the physician office among individuals of all ages. The Behavioral Risk Factor Surveillance System (BRFSS) collects data each year from the 50 states, the District of Columbia, and 3 United States territories to provide prevalence data for state and local health department asthma programs. Findings from BRFSS indicated that approximately 7.2 % of adults in the United States have current asthma (CDC, 2003). According to the National Heart, Lung and Blood Institute's (2002) global strategy for asthma management and prevention, the preferred therapy for patients with moderate persistent asthma is regular treatment with a combination of inhaled corticosteroids and a long-acting inhaled beta 2-agonist twice-daily. For patients with severe persistent asthma, the primary therapy includes inhaled corticosteroid at higher doses plus a long-acting inhaled beta 2-agonist twice-daily.
Bronchial thermoplasty (BT) is a bronchoscopic procedure that employs radiofrequency ablation to reduce the mass of airway smooth muscle (ASM), thus attenuating bronchoconstriction. It is being studied as a minimally invasive method to improve asthma control. Bronchial thermoplasty is performed on an out-patient basis with conscious sedation (i.e., no general anesthesia is needed), and it usually takes approximately one hour to complete. There are 2 assumptions that underlie the development of this procedure: (i) ASM is a vestigial tissue; and (ii) treatment directed at ASM alone will provide sustained symptomatic and physiological improvement in patients with asthma.
Mitzner (2006) discussed the potential of BT in preventing serious consequences resulting from asthma. The most important factor in minimizing an asthmatic attack is limiting the degree of smooth muscle shortening. The premise that ASM can be either inactivated or obliterated without any long-term alteration of other lung tissues, and that airway function will remain normal, albeit with reduced bronchial constriction, has been demonstrated in dogs, a subset of normal subjects, as well as mild asthmatics. Bronchial thermoplasty may thus develop into a useful clinical procedure to effectively impair the ability for ASM to reach the levels of pathological narrowing that characterizes an asthma attack. It may also enable more successful treatment of asthma patients who are unresponsive to more conventional therapies. Whether this will remain stable for the lifetime of the patient still remains to be determined, but at the present time, there are no indications that the smooth muscle contractility will return. This preliminary experience showing that BT could be safely performed in patients with asthma has led to an ongoing clinical trial at a number of sites in Europe and North America designed to examine the effectiveness of this procedure in subjects with moderately severe asthma.
In a prospective study, Miller et al (2005) evaluated the feasibility and safety of BT in the human airway, and determined if the reduction in ASM observed in animal studies could be replicated. A total of 9 patients scheduled to undergo lung resection for suspected or proven lung cancer received BT during routine pre-operative bronchoscopy up to 3 weeks prior to pre-scheduled lung resection. Treatment was limited to areas of the segmental bronchi within the lobe that was to be removed. Treated airways were inspected via bronchoscopy at the time of thoracotomy, and were examined histologically following surgical resection. There were no adverse clinical effects of the procedure, including no new symptoms and no unscheduled visits for medical care. Treated sites exhibited slight redness and edema of the mucosa within 2 weeks of treatment, and appeared normal at later time points. There was narrowing (visually estimated at 25 to 50 %) in four airways in 2 subjects examined at 5 days and 13 days after treatment, with excess mucus in two of these airways. There was no bronchoscopic evidence of scarring in any of the airways examined. Histological examination showed a reduction in ASM, and the extent of the treatment effect was confined to the airway wall and the immediate peri-bronchial region. The authors concluded that BT to the human airway appears to be well-tolerated, and treatment resulted in significant reduction of smooth muscle mass in the airways. They noted that BT may provide therapeutic benefit in disease states such as asthma.
Cox et al (2006) examined the safety and impact on lung function and airway responsiveness of BT over 2 years in 16 subjects with mild-to-moderate asthma. Baseline and 12-week post-treatment measurements included spirometry, methacholine challenge, daily diary recordings of peak flow, symptoms, and medication usage. Subjects completed follow-up evaluations at 12 weeks, 1 year, and 2 years. The procedure was well-tolerated; side effects were transient and typical of what is commonly observed after bronchoscopy. All subjects reported improvement in airway responsiveness. The mean PC(20) increased by 2.37 +/- 1.72 (p < 0.001), 2.77 +/- 1.53 (p = 0.007), and 2.64 +/- 1.52 doublings (p < 0.001), at 12 weeks, 1 year, and 2 years post-procedure, respectively. Data from daily diaries collected for 12 weeks indicated significant improvements over baseline in symptom-free days (p = 0.015), morning peak flow (p = 0.01), and evening peak flow (p < or = 0.007). Spirometry measurements remained stable throughout the study period. The authors concluded that BT is well-tolerated in patients with asthma and results in decreased airway hyper-responsiveness that persists for at least 2 years. Limitations of this case series includes its small size, lack of comparison group, and limited duration of followup. In an editorial that accompanied the afore-mentioned article, Bel (2006) noted that "[w]hether bronchial thermoplasty will earn a place in the treatment of asthma remains to be determined. However, this study shows the potential for a completely new approach of treating asthma and stimulates the development of new hypotheses".
Cox and colleagues (2007) examined the effect of BT on the control of moderate or severe persistent asthma. These researchers randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta 2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either BT or a control group. The primary outcome was the frequency of mild exacerbations, calculated during 3 scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed. The mean rate of mild exacerbations, as compared with baseline, was reduced in the BT group but was unchanged in the control group (change in frequency per subject per week, -0.16 +/- 0.37 versus 0.04 +/- 0.29; p = 0.005). At 12 months, there were significantly greater improvements in the BT group than in the control group in the morning peak expiratory flow (39.3 +/- 48.7 versus 8.5 +/- 44.2 L/min), scores on the AQLQ (1.3 +/- 1.0 versus 0.6 +/- 1.1) and ACQ (reduction, 1.2 +/- 1.0 versus 0.5 +/- 1.0), the percentage of symptom-free days (40.6 +/- 39.7 versus 17.0 +/- 37.9), and symptom scores (reduction, 1.9 +/- 2.1 versus 0.7 +/- 2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the 2 groups. Adverse events immediately after treatment were more common in the BT group than in the control group but were similar during the period from 6 weeks to 12 months after treatment. The authors concluded that BT in subjects with moderate or severe asthma results in an improvement in asthma control. Limitations of the study included the lack of blinding. In addition, the primary study outcomes of bronchial thermoplasty occured during a period of withdrawal of LABA per study protocol, which does not reflect how asthma is managed in standard clinical practice. The small increment in improvement quality of life with BT compared to the control group was of questionable clinical significance. The rate of severe adverse reactions where higher (3 percent) in the BT group compared to the control group (1 percent). The BT group also had more hospitalizations for respiratory causes (9) than the control group (5). In an editorial that accompanied the afore-mentioned article, Solway and Irvin (2007) stated that "[b]ronchial thermoplasty represents a novel approach to targeting airway smooth muscle, but it ablates airway myocytes only in bronchi 3 mm or larger in diameter, which can be treated directly. For this reason, and because of the considerable effort involved (three separate bronchoscopic procedures, each with a small but significant risk of complications), notable adverse effects (in the short term, at least), and likely expense, bronchial thermoplasty will probably need further refinement if it is to emerge as a widely applicable, practical treatment for moderate or severe asthma. Nonetheless, the results reported by Cox and colleagues suggest that we should now contemplate other approaches to targeting airway smooth muscle that might prove to be less invasive, more practical, and more amenable to application throughout the airways".
In a subsequent publication (Thomson, et al., 2011a), the investigators continued to follow the BT group for a total of five years and the control group for a total of three years. Patients enrolled in the AIR Trial were on inhaled corticosteroids greater than or equal to 200 μg beclomethasone or equivalent plus long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4-year safety study. Adverse events and spirometry data were used to assess long-term safety out to 5 years post-BT. A total of 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years, respectively. The rate of respiratory AEs per subject was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in years 2, 3, 4, and 5 compared to year 1. The FVC and FEV1 values showed no deterioration over the 5-year period in the BT group. Similar results were obtained for the control group. The authors concluded that absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of forced vital capacity and FEV(1) over a 5-year period post-BT in this group of patients with moderate-to-severe asthma support the long-term safety of the procedure out to 5 years. However, it is interesting to note that similar results were obtained in the control group. During the three years of long-term follow-up with data comparing the two groups there were no differences in the clinically relevant outcomes: hospitalizations, emergency room visits, and oral steroids to treat respiratory exacerbations. Although the outcomes of this study suggest that the benefits of BT persist and no unexpected respiratory pathologies develop, the sample size was small, so considerable uncertainty remains.
Pavord et al (2007) examined the safety and effectiveness of BT in patients with symptomatic, severe asthma. Adults who were symptomatic despite treatment with fluticasone or equivalent at more than 750 mug/day and other medications, which could include 30 mg or less of oral prednisolone/day, were randomized to BT or to a control group. After treatment, subjects entered a 16-week steroid stable phase (weeks 6 to 22), a 14-week steroid wean phase (weeks 22 to 36), and a 16-week reduced steroid phase (weeks 36 to 52). Bronchial thermoplasty resulted in a transient worsening of asthma symptoms. Seven hospitalizations for respiratory symptoms occurred in 4 of 15 patients who received BT during the treatment period. Five hospitalizations were within 3 days of treatment. Two subjects had segmental collapse involving the most recently treated lobe; 1 required bronchoscopy and aspiration of a mucus plug. There were no hospitalizations during this period in the 17 control subjects. The rate of hospitalizations was similar in both groups in the post-treatment period. At 22 weeks, patients who received BT had significant improvements versus control subjects in rescue medication use (-26.6 +/- 40.1 versus -1.5 +/- 11.7 puffs/7 day, p < 0.05), pre-bronchodilator forced expiratory volume in 1 second [FEV(1)] % predicted (14.9 +/- 17.4 versus -0.94 +/- 22.3 %, p = 0.04), and Asthma Control Questionnaire scores (-1.04 +/- 1.03 versus -0.13 +/- 1.00, p = 0.02). Improvements in rescue medication use and ACQ scores remained significantly different from those of controls at 52 weeks. The authors concluded that BT is associated with an excess of hospitalizations and a short-term increase in asthma-related morbidity. However, there is preliminary evidence of long-lasting improvement in asthma control. However, the results of this study may be biased because it was a small trial with large imbalances in important participant characteristics at baseline. The study is also limited because of lack of blinding.
Wechsler (2008) noted that BT holds promise in the management of patients with asthma. Herth (2008) stated that a short-term increase in morbidity due to bronchoscopy is to be expected with BT. The author noted that further trials are needed to investigate the value of this method, particularly with regard to long-term effects. Jesudason (2009) stated that BT is a new treatment for refractory asthma. However, the mechanism of its effects is unclear.
In a review on BT for the treatment of asthma, Martin and Pavord (2009) concluded that applying thermal energy to the airway in the form of BT results in the selective destruction of ASM; this is replaced by fibrous connective tissue. In early animal and human studies, this was associated with a reduction in objective measurements of asthma control, such as airway hyper-responsiveness (AHR). However, in the 2 published RCTs on this technique, there has been a failure to show improvements in AHR, although there have been significant improvements in more subjective measurements of asthma control. Neither trial was blinded, and concern remains about a significant placebo effect of the treatment. The Asthma Intervention Research 2 (AIR2) Trial, which is randomized and blinded with a sham treatment arm, has been designed to try to address these issues in more detail.
In randomized sham-controlled clinical study of BT in patients with refractory asthma (AIR2 study), Castro et al (2010) reported a significant improvement in Asthma Quality of Life scores in patients treated with bronchial thermoplasty. However, subjects assigned to a sham procedure also experienced a significant improvement from baseline, such that the difference between subjects treated with BT versus subjects treated with a sham procedure was of questionable clinical significance. In this study funded by Asthmatx, Castro et al (2010) reported on a study to evaluate the effectiveness and safety of BT versus sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta 2-agonists. In this study, 288 adult subjects were randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in a Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). The AQLQ is a 7-point Likert scale, where a 0.5 change in score is considered the minimally important difference. Subjects assigned to BT had an average 1.35 +/- 1.10 improvement over baseline in integrated AQLQ score. However, subjects assigned to a sham procedure had an average 1.16 +/- 1.23 improvement over baseline. There were more respiratory adverse events in the BT group during the initial treatment period including an excess of hospitalizations. After the initial treatment period, there was a reduction in ER visits, but not in hospitalizations for the BT group compared to the sham group.
An editorial that accompanied the afore-mentioned study by Castro et al, Bel (2010) noted that "[t]he trial demonstrated that 6 to 12 months after the procedure, bronchial thermoplasty had a small, but significantly greater mean positive effect on the asthma-related quality of life score than did the sham procedure. The mean difference in score was 0.19, which was statistically significant but substantially smaller than the minimum clinically important difference of 0.5. Remarkably, not one of the secondary outcomes showed a difference between bronchial thermoplasty and sham procedure. Additional outcomes that were collected to assess safety showed that during the post-treatment period there were less severe exacerbations and emergency room visits in the bronchial thermoplasty group compared with the sham control group, but over the entire study period there was no difference in outcomes between the groups". Furthermore, Bel (2010) stated that "[t]he overall net effect of bronchial thermoplasty in the AIR2 trial is somewhat disappointing. Although airway hyperresponsiveness as a most relevant outcome of bronchial thermoplasty is difficult to measure in patients with severe asthma, one would have hoped to see at least an effect on asthma control, use of rescue medication, or pre/post-bronchodilator FEV1. This was not the case. Instead, the authors observed a reduction in the rate of severe exacerbations and emergency department visits in the post-treatment period. This safety outcome was completely unexpected and was not considered in the rationale and hypothesis of the study. How can this be explained in the absence of any improvement in asthma control? Does it suggest that bronchial thermoplasty has more effects than just inactivating the airway smooth muscle? Does it suggest that the procedure might alter the inflammatory or neurogenic responses to viral infection or other triggers of asthma exacerbations?" On the question of whether BT should be offered to patients with severe asthma, Bel (2010) stated that "[f]or patients with uncontrolled asthma who have not been submitted to a rigorous treatment protocol, the answer is no. For the remaining patients, the AIR2 results might offer some hope. Bronchial thermoplasty appears to have a benefit on the quality of life and severe exacerbations. Importantly, severe asthma has many phenotypes, and at present we have no clue which phenotype will benefit the most. It is inevitable that phenotypic targeting will be essential for this invasive procedure. Moreover, we need to know how durable the benefit will be to ensure that the benefits outweigh the risks and burden of the procedure. Therefore, long-term clinical and morphological research in various severe-asthma phenotypes is still needed to obtain the required information for clinical decisions".
Torrego Fernández (2010) stated that despite the numerous guidelines and treatments available for asthma, the disease remains poorly controlled in some patients, who remain symptomatic, are a considerable burden on the health system, and account for most of the hospitalizations due to asthma. Bronchial thermoplasty is a novel experimental therapeutic option that consists of delivering radiofrequency-generated heat to the airways via a catheter inserted in the bronchial tree through a flexible bronchoscope to reduce smooth muscle quantity and contractility. The first investigations were conducted using an animal model. Subsequently, 2 RCTs designed to evaluate the safety and efficacy of BT in patients with moderate-to-severe asthma with a 1-year follow-up period showed the procedure to be safe, with mostly transient adverse affects and several clinical benefits. Although results from ongoing clinical trials are still awaited, BT may become an innovative therapeutic approach to asthma.
Cox (2010) noted that asthma can be provoked by a wide range of stimuli that include infectious, allergic, and environmental agents. Broncho-constriction determines much of the short-term variability in airflow that characterizes asthma. Current treatments do not redress the excess smooth muscle mass that is present in the re-modeled airway in chronic asthma. Thus, it is intriguing to consider the potential contribution ofBT as a treatment for poorly controlled asthma.
In April 2010, the FDA approved the Alair Bronchial Thermoplasty System (Asthmatx Inc., Sunnyvale, CA) for the treatment of patients aged 18 and older whose severe and persistent asthma is not well-controlled with inhaled corticosteroids and long-acting beta agonist medications. The FDA based its approval on data from a clinical trial of 297 patients with severe and persistent asthma. The trial showed a reduction of severe asthma attacks with use of the Alair system. Moreover, the FDA is requiring a 5-year post-approval study of the device to study its long-term safety and effectiveness. Asthmatx will follow many of the patients who were enrolled in the clinical trial and enroll 300 new patients at several medical centers across the United States.
Possible side effects during the course of treatment may include anxiety, asthma attacks, atelectasis, chest tightness or pain, headaches, hemoptysis, nausea, and wheezing. While the Alair system is designed to reduce the number of severe asthma attacks on a long-term basis, there is a risk of immediate asthma attacks during the course of the treatment. Furthermore, the Alair system is not for use in asthma patients with a pacemaker, internal defibrillator, or other implantable electronic device. Also, those patients with known sensitivities to lidocaine, atropine, or benzodiazepines should not use the device. Alair has not been studied for success in re-treatment of the same area of the lung. Currently, patients should not be re-treated with the Alair system in the same area of the lung. In addition, asthma patients considering the Alair system should not be treated while the following conditions are present: an active respiratory infection, asthma exacerbations, coagulopathy, or if they have had changes to their corticosteroid regimen 14 days before the proposed treatment.
Castro and colleagues (2011) examine the persistence of effectiveness of BT 2 years post-treatment in subjects with severe asthma. Subjects participating in the long-term safety follow-up phase of the AIR2 Trial were evaluated by comparing the proportion of subjects who experienced exacerbations, adverse events (AEs), or healthcare utilization during the first year (year 1) after BT with the proportion of subjects who experienced the same during the subsequent 12 months (year 2). Severe exacerbations, respiratory AEs, emergency department visits for respiratory symptoms, and hospitalizations for respiratory symptoms (proportion of subjects experiencing and rates of events), and stability of pre- and post-bronchodilator FEV(1), were comparable between years 1 and 2. The proportion of subjects experiencing severe exacerbations in year 2 after BT was 23.0 %, compared with 30.9 % in year 1. The authors concluded that reduction in the proportion of subjects experiencing severe exacerbations after BT is maintained for at least 2 years.
It is also interesting to note in a recent review by Thomson et al (2011b), BT is listed as one of the emerging therapeutic option for severe asthma. This is in agreement with Colice (2011) who also listed BT as an emerging therapy for asthma. Colice concluded that although more studies are needed to examine the safety and effectiveness of both pharmacological and non-pharmacological approaches including BT, there is future promise for therapeutic advances in severe, persistent asthma. Furthermore, Oliveinstein et al (2011) reviewed alternative therapeutic strategies in the management of severe asthma including macrolide antibiotics, biologic agents, modulators of signal transduction pathways and BT. The authors noted that the challenge remains to determine the appropriate phenotype for each therapeutic strategy in view of the heterogeneity of severe asthma.
Wu and associates (2011) performed a meta-analysis of the safety and effectiveness of BT in patients with moderate-to-severe persistent asthma. An electronic literature search identified 3 RCTs of BT that recruited a total of 421 patients. Outcomes of interest were the AQLQ score, morning PEF, tolerability and safety. Compared with standard medications and sham-bronchial thermoplasty, BT significantly improved AQLQ scores and PEF from baseline to the end of the trials. There were more respiratory AEs and hospitalizations for adverse respiratory events with BT than with medications or sham-treatment during the treatment period, but most events resolved, on average, within 1 week. This effect of BT was not seen during the post-treatment period. The authors concluded that additional long-term RCT are needed to confirm whether BT provides benefit to patients with moderate-to-severe persistent asthma.
The National Horizon Scanning Centre (2011) has stated: "Further longer-term safety data and data on the effect of bronchial thermoplasty on long term health outcomes such as hospitalisation rates, GP consultation rates, medication use and quality of life are awaited. Research into the exact mechanism through which the device may work and in predicting which patients are most likely to respond to this treatment is required"
The Institute for Clinical Systems Improvement's practice guideline on diagnosis and management of asthma (ICSI, 2010) does not mention the use of BT.
The California Technology Assessment Forum (Tice, 2011) concluded that use of bronchial thermoplasty for the treatment of severe, refractory asthma meets CTAF TA Criterion 1 through 5 for safety, effectiveness and improvement in net health outcomes. The CTAF assessment noted that the most important trial of BT to consider is the AIR2 trial, because it was the only trial that used a sham control to blind patients and they also ensured that staff assessing patient outcomes remained blinded to patient allocation. The CTAF assessment found a slightly greater improvement in quality of life in the BT group compared to the sham group in the AIR2 trial, but it did not meet the pre-specified criteria for statistical or clinical significance. However, the CTAF panel felt that the net improvements were sufficient in this patient population with few options. The CTAF assessment concluded that there remain some concerns about the long-term sequelae of BT, as the number of patients followed out for five years and longer is relatively small, so there may be some uncommon long-term harms that have yet to be identified.
Guidelines from the Global Initiative for the Evaluation and Management of Asthma, updated in December 2011, state: "For adult patients whose asthma remains uncontrolled despite application of this therapeutic paradigm and referral to an asthma specialty center, bronchial thermoplasty is now a possible option in some countries. In this bronchoscopic treament, airways are treated on three occasions with a localized radiofrequency pulse. The treatment, which itself is associated with asthma exacerbations in the months post bronchoscopy, results in a subsequent decreas in exacerbations. There are no significant effects on lung function or asthma symptoms. The safety and efficacy of thermoplasty beyond one year is not known. Caution should be used in selecting patients for this procedure." The Global Initiative for Asthma (GINA) was launched in conjunction with the World Health Organization and the National Heart, Lung and Blood Institute.
The National Institue for Health and Clinical Excellence (NICE, 2012) issued guidance on BT for severe asthma, which states that evidence on the safety of BT is adequate in the short- and medium-term, although patients may experience exacerbation of symptoms after the procedure. The guidance states that more evidence is required on the safety of the procedure in the long-term. The guidance notes that, with regard to efficacy, there is some evidence of improvement in symptoms and quality of life but objective evidence of improved lung function is inadequate. NICE recommends, therefore, that this procedure should only be used with special arrangements for clinical governance, consent and audit or research. Specialist Advisors to NICE stated that improvement in symptoms and quality of life, and reductions in exacerbations and in the need for admission to hospital were more relevant efficacy outcomes than the results of lung function tests. The NICE Committee noted that many patients are young and it is therefore particularly important to monitor them for any possible long-term adverse effects such as development of bronchial stenosis.
In a review on the future of chronic obstructive pulmonary disease (COPD) treatment, Martinez and colleagues (2011) listed several novel non-pharmacotherapies including creation of arterio-venous fistulas, endobronchial glue, endobronchial thermal vapor, insertion of endobronchial valves, non-invasive mechanical ventilation, and transcutaneous electrical stimulation. Bronchial thermoplasty is not mentioned as a possible therapeutic option. Furthermore, the Institute for Clinical Systems Improvement's practice guideline on diagnosis and management of COPD (ICSI, 2011) does not mention the use of BT.
James and Gupta (2011) stated that even with the use of maximum pharmacological treatment, asthma still remains uncontrolled in some cases. For such cases of uncontrolled asthma, a novel therapy, BT, has shown some promising results over the past few years. Three major trials of BT showed that it does not cause any improvement in FEV1. However, BT improved the quality of life and decreased the future exacerbations and emergency hospital visits due to asthma. But the benefit observed was too small to be clinically significant. Follow-up (2 to 5 years) results of these BT trials did not show any significant long-term adverse event related to BT. However, further independent large RCTs and results of application of BT in real hospital settings are needed to define its role in asthma management.
On behalf of the British Thoracic Society, Du Rand and colleagues (2011) published a guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Regarding the use of BT the guideline noted that it is a possible treatment option in selected patients with severe persistent asthma already on maximal therapy, although its place in the treatment of asthma remains to be established. The authors also noted that the long-term safety and effectiveness of this procedure remain unclear. Hence treatment should be limited to a few specialized centers in carefully selected patients. They stated that longer-term follow-up of treated patients is needed.
Boulet and Laviolette (2012) stated that BT has been shown to reduce asthma exacerbations, and improve asthma control and quality of life over a 3-year period without significant complications up to a 5-year period. It could be considered as another option in the treatment of selected patients requiring oral and/or high doses of inhaled corticosteroids to control asthma. It should, however, be performed in specialized centers in patients who understand the potential benefits and side-effects of this technique. The response to this treatment varies from one patient to another. The authors concluded that further studies are needed to better-define the role of this option in the treatment of asthma.
Wahidi and Kraft (2012) stated that RCTs of BT in severe asthma have not been able to show a reduction in airway hyper-responsiveness or change in FEV(1), but have suggested an improvement in quality of life, as well as a reduction in the rate of severe exacerbations, emergency department visits, and days lost from school or work. Strict inclusion and exclusion criteria of these trials resulted in the elimination of patients with severe asthma who experienced more than 3 exacerbations per year. Therefore, the generalizability of this treatment to the broader severe asthma population still needs to be determined. The short-term adverse events consist primarily of airway inflammation and occasionally more severe events requiring hospitalization. Long-term safety data are evolving and have shown thus far clinical and functional stability up to 5 years after BT treatment. The authors concluded that additional studies on BT are needed to establish accurate phenotyping of positive responders, durability of effect, and long-term safety.
In a review on "Severe asthma: Future treatments" O'Byrne et al (2012) stated that BT may provide benefit in improving control and reducing exacerbations in selected patients. The addition of the muscarinic antagonist, tiotropium also improves airflow obstruction, but its benefit on exacerbation risk is not yet established. Other developments being evaluated in severe refractory asthma are CXCR2 antagonists in patients with a persisting neutrophilic airway inflammation, and CRTh2 antagonists, both of which are small molecule antagonists, and hMabs against IL4 and IL-13. Finally, other approaches to reduce receptor numbers, using inhaled anti-sense, has shown to reduce allergen-induced airway eosinophilia, and combining different anti-sense against different targets may become a feasible treatment option. A variety of new treatment options are being investigated to help improve overall asthma control in patients with severe refractory asthma. These include medications to optimize lung function; BT to reduce airway smooth muscle in central airways; and those which target specific inflammatory cells or receptors of inflammatory mediators.
In summary, although available data are promising, more research is needed to ascertain what role, if any, BT should play in the treatment of patients with asthma. Furthermore, there is a lack of evidence regarding the effectiveness of BT in the management of patients with chronic obstructive pulmonary disease.