The efficacy and safety of bronchial thermoplasty in severe persistent asthma on extended follow-up

The efficacy and safety of bronchial thermoplasty in severe persistent asthma on extended follow-up Abstract Background Asthma is a common condition and there remains a subset of patients who are poorly controlled on maximal therapy. Bronchial thermoplasty (BT) is a bronchoscopic therapy using radiofrequency energy to reduce airway smooth muscle, which has been shown to improve asthma control although further evidence regarding long-term efficacy and safety is required. Aim We aimed to demonstrate safety and efficacy of BT on extended follow-up. Our initial experience with this group was previously reported in 2016, where patients were shown to have a significant improvement in asthma control test (ACT) scores 1-year post-treatment. Design We carried out a retrospective observational study of seven patients who underwent BT between 2012 and 2013 in an Irish severe asthma centre. The primary endpoint was change in ACT scores from baseline to present. Methods Seven patients underwent BT at a tertiary referral centre in Ireland. ACT scores and data on hospital admissions, exacerbations, maintenance corticosteroid requirements, rescue bronchodilator use and forced expiratory volume for 1 s (FEV1) prior to the procedure and on extended follow-up were collected. Mean follow-up was 49.42 months. Results A trend towards improvement was seen in median hospitalisations (respective values for median over 12 months 3, 1 P = 0.059) and ACT scores, from 9 to 13 (P = 0.249). Mean FEV1 was 1.68 l prior to treatment and 1.46 l 4 years post-treatment (P = 0.237). There was no mortality among the group. Conclusions These data support the safety of BT and suggest extended efficacy. Introduction Asthma is an extremely common condition affecting more than 235 million people worldwide. In Ireland, we have the fourth highest prevalence in the world, more than one person a week dies from asthma and 14% of asthmatics attend emergency services each year1 leading to an estimated 20 000 emergency department attendances and over 5000 hospital admissions annually.2 While regular inhaled medications control symptoms in the majority of patients there remains a subset who are uncontrolled leading to significant symptom burden, exacerbations and lost school and work days. Thirty-seven percentage of asthmatics in Ireland miss work or school with adults missing an average of 12 work days and children missing an average of 10 school-days per year.3 These patients require a disproportionate quantity of healthcare resource and there is a persistent requirement for more therapeutic options. Bronchial thermoplasty (BT) is an emerging therapy which is included in global initiative for asthma (GINA) guidelines at Step 5 for patients who remain uncontrolled despite optimised treatment regimens and referral to an asthma specialty centre.4 BT uses radiofrequency thermal energy to reduce airway smooth muscle (ASM) mass, therefore, aiming to reduce airway hyperresponsiveness. This may lead to a reduction in symptoms and exacerbation frequency. BT has been shown to reduce severe exacerbation rates and emergency visits5 and this effect was maintained on 5 years of follow-up.6 While, BT is included in the GINA guidelines, the group does recommend that patients should be carefully selected, and further study is required with regard to safety and efficacy. In this study, we aimed to demonstrate the safety and efficacy of BT on extended follow-up, we describe the outcomes of seven patients who were treated with BT in a severe asthma centre after extended follow-up. Our initial experience with this group was previously reported in 2016, where patients were shown to have a significant improvement in asthma control test (ACT) scores 1 year post-treatment.7 Design A retrospective observational study of seven patients who underwent BT between 2012 and 2013 in an Irish severe asthma centre was conducted. The primary endpoint was change in ACT scores from baseline to present. The ACT is a five-item questionnaire relating to asthma control, with each item scored from one to five, with a higher score representing better control to a maximum of 25. Secondary endpoints were changes in hospital admission and exacerbation frequency, maintenance oral corticosteroid requirement, rescue bronchodilator use and forced expiratory volume for 1 s (FEV1). An exacerbation was defined as poorly controlled symptoms leading to an increase in reliever usage, commencement of oral steroid or antibiotics, emergency department visit or hospitalisation. Methods Seven patients who fulfilled inclusion criteria were identified. The patients’ mean age was 55.6 (standard deviation 14). Six had never smoked, one was an ex-smoker. Five were female. Their mean body mass index was 29.7 (standard deviation 5.3). Their mean FEV1 was 1.68 l (0.8 l–2.43 l). All seven patients remained poorly controlled despite treatment according to Step 4 of the Global Institute for Asthma Guidelines. Five were ‘steroid dependant’ and were maintained on an average of 16 mg of prednisone daily. Two patients were omalizumab responders and four had not responded. Mean follow-up was 49.42 months (min 39, max 59). Prior to referral for BT, patients were reviewed with regard to asthma control indicators, compliance, pharmacotherapy regimens, allergy testing, education including avoidance of precipitants and inhaler technique and smoking cessation as necessary. Patients were instructed to maintain peak flow diaries for a period not <3 months so as to maximise compliance with prescribed medications including omalizumab and subcutaneous terbutaline pump where appropriate. Patients whose control remained poor were offered referral for BT. The patients were pre-admitted to an elective admissions unit to ensure stability prior to the procedure. All patients were prophylactically commenced on high dose corticosteroids and underwent spirometry on the day of the procedure. The procedure took place over three treatment sessions, treating the right lower lobe, the left lower lobe and both upper lobes respectively. Clinical data relating to the patients’ ACT score, maintenance corticosteroid use, rescue bronchodilator use, exacerbation frequency and hospital admissions during the 12 months prior to BT and the last 12 months were collected by retrospective chart review and patient interview. Repeat spirometry was performed prebronchodilators in all except one patient who declined spirometry. Statistical analysis undertaken using Minitab version 17 using the Wilcoxon Signed Rank test. Differences were considered statistically significant at P < 0.05. Results The median ACT score improved from 9 [interquartile range (IQR) 4] before BT to 13 (IQR 13) after 4-year follow-up (Fig. 1). This did exceed the minimally clinically important difference (MCID) of three however, this was not statistically significant (P = 0.249, Wilcoxon Signed Rank). Hospital admissions improved from a median of 3 (IQR 4) in the year prior to BT to 1 (IQR 2) in the last year (Fig. 2), a difference which trended towards statistical significance (P = 0.059). Admission rates for individual subjects are shown in Fig. 3. The overall median exacerbation rate showed only a modest improvement from 5 (IQR 3)–4 (IQR 6) (P = 0.402). There was an increase in maintenance oral corticosteroid requirement from prior to BT, median 10 mg (IQR 30 mg), to 4 years post-BT, median 20 mg (IQR 25 mg) (P = 1.000). There was a small reduction in mean FEV1 from 1.68 l prior to BT to 1.46 l 4 years post-procedure however this was not statistically significant (P = 0.463) Fig. 4. There was no mortality among the group. Figure 1 View largeDownload slide Median Asthma Control Test (ACT) scores pre and post Bronchial Thermoplasty. Figure 1 View largeDownload slide Median Asthma Control Test (ACT) scores pre and post Bronchial Thermoplasty. Figure 2 View largeDownload slide Median yearly admission rate pre and post Bronchial Thermoplasty. Figure 2 View largeDownload slide Median yearly admission rate pre and post Bronchial Thermoplasty. Figure 3 View largeDownload slide Yearly admission rate per patient pre and post Bronchial Thermoplasty. Figure 3 View largeDownload slide Yearly admission rate per patient pre and post Bronchial Thermoplasty. Figure 4 View largeDownload slide Prebronchodilator FEV1 per patient pre and post Bronchial Thermoplasty. Figure 4 View largeDownload slide Prebronchodilator FEV1 per patient pre and post Bronchial Thermoplasty. Conclusions The function of ASM has been subject to debate for many years, multiple roles in normal function have been postulated including immunomodulation, extracellular matrix deposition and regulation of bronchomotor tone8 with some claiming it is a vestigial structure without an essential function.9 It has been shown that asthmatics have an increased volume of ASM compared with normal controls and those with fatal asthma have increased ASM cell hyperplasia when compared to subjects with non-fatal asthma.10 In severe asthma, the increased ASM contributes to bronchoconstriction, airway inflammation and airway remodelling. It is, therefore, reasonable to suggest that a reduction in ASM could potentially improve bronchoconstriction and airway remodelling leading to better asthma control. BT targets ASM by using thermal energy to reduce ASM mass and its contractility, all airways distal to the mainstream bronchi between 3 and 10 mm in diameter are treated except in the right middle lobe.11 The manufacturer advises against treatment of the right middle lobe due to the narrow diameter of the lobar bronchus and its acute take-off angle, characteristics which may promote atelectasis or difficulty in re-inflation if transient obstruction occurs as a result of procedure-related inflammation or oedema. Although bronchoconstriction occurs throughout the bronchial tree in asthma, and it is not certain what the relative contribution of central and peripheral airways to airflow obstruction is, the greatest source of resistance to airflow in the normal bronchial tree is in the conducting airways at about the fourth generation.12 Therefore it is likely that narrowing in this area would cause a greater effect to overall airflow obstruction and treating more central airways should have a therapeutic effect. Although our patient group is small, we have shown an enduring reduction in hospital admission rates after 4 years of follow-up which trends towards statistical significance. This translates into a significant benefit for our patient group with regard to quality of life and a reduction in healthcare costs associated with their asthma. The National Health Service in the United Kingdom estimates costs associated with an emergency admission at over €120013 while lost work days also carry a significant economic burden. Our initial study on these patients showed a significant improvement in ACT scores in this study we could not show a statistically significant improvement in ACT so persistence of efficacy was not demonstrated however the improvement did reach the MCID which is encouraging. While BT is included in GINA guidelines,4 it should be noted that caution is advised in selecting patients, and they note that longer-term follow-up is needed with regard to effectiveness and safety. They advise that BT is an option for patients whose asthma remains uncontrolled despite optimised therapeutic regimens and referral to an asthma specialty centre.4 Our patient group were all assessed in a severe asthma centre and underwent a minimum of 3 months of close supervision with maintenance medications prior to the procedure in order to ensure compliance with medications, only when optimised according to GINA guidelines did we proceed to thermoplasty. Reassuringly there was no significant drop in FEV1 in our patient group and no mortality. This is especially reassuring given that the original sham controlled study excluded patients with an FEV1 <60%5 whereas our group included patients with severe disease several of whom had FEV1 <60% and many were frequent exacerbators. This is a valuable contribution to our knowledge regarding safety of BT. This study adds to our experience of BT for the treatment of severe asthma. Our initial data from this group 1 year post-intervention showed a statistically significant improvement in the ACT scores and a reduction in hospital admissions which trended towards statistical significance. Here we have shown durability of effect of the treatment and safety of the procedure which is consistent with international data.7 BT warrants ongoing study as although it is an invasive, relatively costly intervention it provides therapeutic options in a population who are currently difficult to treat and alternative emerging asthma therapy also carry a significant financial burden. Further characterization of the asthma sub-phenotypes who are likely to exhibit the greatest clinical benefit from BT would be helpful in the management of severe asthma. Conflict of interest: None declared. References 1 Manning P, Shanahan E, O'Connor T, Elnazir B, Ni Chroinin M, Williams N, et al.   A multicentre programme in primary care to evaluate current asthma control among patients and examine barriers and facilitators to the implementation of evidence based GINA asthma guidelines in the Republic of Ireland (RoI). Ir J of Med Sci  2010; 179: S478. 2 Central Statistics Office. Report on Vital Statistics 2002 to 2010. Dublin, Stationary Office, 2010. 3 Weiss KB, Sullivan SD. The health economics of asthma and rhinitis. 1 Assessing the economic impact. J Allergy Clin Immunol  2001; 107: 3– 8. Google Scholar CrossRef Search ADS PubMed  4 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2017. www.gina.org (30 May 2017, date last accessed). 5 Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, et al.  ; AIR2 Trial Study Group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med  2010; 181: 116– 24. http://dx.doi.org/10.1164/rccm.200903-0354OC Google Scholar CrossRef Search ADS PubMed  6 Castro M, Rubin A, Laviolette M, Hanania NA, Armstrong B, Cox G; AIR2 Trial Study Group. Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma. Ann Allergy Asthma Immunol  2011; 107: 65– 7. Google Scholar CrossRef Search ADS PubMed  7 Watchorn DC, Sahadevan A, Egan JJ, Lane SJ. The efficacy of bronchial thermoplasty for severe persistent asthma: the first national experience. Ir Med J  2016; 109: 406. Google Scholar PubMed  8 Panettieri RA, Kotlikoff MI, Gerthoffer WT, Hershenson MB, Woodruff PG, Hall IP, et al.   Airway smooth muscle in bronchial tone, inflammation, and remodeling. Am J Respir Crit Care Med  2008; 177: 248– 52. Google Scholar CrossRef Search ADS PubMed  9 Mitzner W. Airway smooth muscle: the appendix of the lung. Am J Respir Crit Care Med  2004; 169: 787– 90. http://dx.doi.org/10.1164/rccm.200312-1636PP Google Scholar CrossRef Search ADS PubMed  10 Carroll N, Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis  1993; 147: 405– 10. http://dx.doi.org/10.1164/ajrccm/147.2.405 Google Scholar CrossRef Search ADS PubMed  11 Cox G, Miller J, McWilliams A, Fitzgerald J, Lam S. Bronchial thermoplasty for asthma. Am J Respir Crit Care Med  2006; 173: 965– 9. Google Scholar CrossRef Search ADS PubMed  12 Hogg JC. The pathology of asthma. APMIS  1997; 105: 735– 45. http://dx.doi.org/10.1111/j.1699-0463.1997.tb05079.x Google Scholar CrossRef Search ADS PubMed  13 National Health Service. Better for Less. https://www.networks.nhs.uk/nhs-networks/respiratory-leads/yorkshire-humber-respiratory-programme/documents/Better%20for%20Less%20-%20%20Asthma%20-Yorks%20-%20Humber.pdf (21 May 2017, date last accessed). © The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png QJM: An International Journal of Medicine Oxford University Press

The efficacy and safety of bronchial thermoplasty in severe persistent asthma on extended follow-up

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© The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Abstract

Abstract Background Asthma is a common condition and there remains a subset of patients who are poorly controlled on maximal therapy. Bronchial thermoplasty (BT) is a bronchoscopic therapy using radiofrequency energy to reduce airway smooth muscle, which has been shown to improve asthma control although further evidence regarding long-term efficacy and safety is required. Aim We aimed to demonstrate safety and efficacy of BT on extended follow-up. Our initial experience with this group was previously reported in 2016, where patients were shown to have a significant improvement in asthma control test (ACT) scores 1-year post-treatment. Design We carried out a retrospective observational study of seven patients who underwent BT between 2012 and 2013 in an Irish severe asthma centre. The primary endpoint was change in ACT scores from baseline to present. Methods Seven patients underwent BT at a tertiary referral centre in Ireland. ACT scores and data on hospital admissions, exacerbations, maintenance corticosteroid requirements, rescue bronchodilator use and forced expiratory volume for 1 s (FEV1) prior to the procedure and on extended follow-up were collected. Mean follow-up was 49.42 months. Results A trend towards improvement was seen in median hospitalisations (respective values for median over 12 months 3, 1 P = 0.059) and ACT scores, from 9 to 13 (P = 0.249). Mean FEV1 was 1.68 l prior to treatment and 1.46 l 4 years post-treatment (P = 0.237). There was no mortality among the group. Conclusions These data support the safety of BT and suggest extended efficacy. Introduction Asthma is an extremely common condition affecting more than 235 million people worldwide. In Ireland, we have the fourth highest prevalence in the world, more than one person a week dies from asthma and 14% of asthmatics attend emergency services each year1 leading to an estimated 20 000 emergency department attendances and over 5000 hospital admissions annually.2 While regular inhaled medications control symptoms in the majority of patients there remains a subset who are uncontrolled leading to significant symptom burden, exacerbations and lost school and work days. Thirty-seven percentage of asthmatics in Ireland miss work or school with adults missing an average of 12 work days and children missing an average of 10 school-days per year.3 These patients require a disproportionate quantity of healthcare resource and there is a persistent requirement for more therapeutic options. Bronchial thermoplasty (BT) is an emerging therapy which is included in global initiative for asthma (GINA) guidelines at Step 5 for patients who remain uncontrolled despite optimised treatment regimens and referral to an asthma specialty centre.4 BT uses radiofrequency thermal energy to reduce airway smooth muscle (ASM) mass, therefore, aiming to reduce airway hyperresponsiveness. This may lead to a reduction in symptoms and exacerbation frequency. BT has been shown to reduce severe exacerbation rates and emergency visits5 and this effect was maintained on 5 years of follow-up.6 While, BT is included in the GINA guidelines, the group does recommend that patients should be carefully selected, and further study is required with regard to safety and efficacy. In this study, we aimed to demonstrate the safety and efficacy of BT on extended follow-up, we describe the outcomes of seven patients who were treated with BT in a severe asthma centre after extended follow-up. Our initial experience with this group was previously reported in 2016, where patients were shown to have a significant improvement in asthma control test (ACT) scores 1 year post-treatment.7 Design A retrospective observational study of seven patients who underwent BT between 2012 and 2013 in an Irish severe asthma centre was conducted. The primary endpoint was change in ACT scores from baseline to present. The ACT is a five-item questionnaire relating to asthma control, with each item scored from one to five, with a higher score representing better control to a maximum of 25. Secondary endpoints were changes in hospital admission and exacerbation frequency, maintenance oral corticosteroid requirement, rescue bronchodilator use and forced expiratory volume for 1 s (FEV1). An exacerbation was defined as poorly controlled symptoms leading to an increase in reliever usage, commencement of oral steroid or antibiotics, emergency department visit or hospitalisation. Methods Seven patients who fulfilled inclusion criteria were identified. The patients’ mean age was 55.6 (standard deviation 14). Six had never smoked, one was an ex-smoker. Five were female. Their mean body mass index was 29.7 (standard deviation 5.3). Their mean FEV1 was 1.68 l (0.8 l–2.43 l). All seven patients remained poorly controlled despite treatment according to Step 4 of the Global Institute for Asthma Guidelines. Five were ‘steroid dependant’ and were maintained on an average of 16 mg of prednisone daily. Two patients were omalizumab responders and four had not responded. Mean follow-up was 49.42 months (min 39, max 59). Prior to referral for BT, patients were reviewed with regard to asthma control indicators, compliance, pharmacotherapy regimens, allergy testing, education including avoidance of precipitants and inhaler technique and smoking cessation as necessary. Patients were instructed to maintain peak flow diaries for a period not <3 months so as to maximise compliance with prescribed medications including omalizumab and subcutaneous terbutaline pump where appropriate. Patients whose control remained poor were offered referral for BT. The patients were pre-admitted to an elective admissions unit to ensure stability prior to the procedure. All patients were prophylactically commenced on high dose corticosteroids and underwent spirometry on the day of the procedure. The procedure took place over three treatment sessions, treating the right lower lobe, the left lower lobe and both upper lobes respectively. Clinical data relating to the patients’ ACT score, maintenance corticosteroid use, rescue bronchodilator use, exacerbation frequency and hospital admissions during the 12 months prior to BT and the last 12 months were collected by retrospective chart review and patient interview. Repeat spirometry was performed prebronchodilators in all except one patient who declined spirometry. Statistical analysis undertaken using Minitab version 17 using the Wilcoxon Signed Rank test. Differences were considered statistically significant at P < 0.05. Results The median ACT score improved from 9 [interquartile range (IQR) 4] before BT to 13 (IQR 13) after 4-year follow-up (Fig. 1). This did exceed the minimally clinically important difference (MCID) of three however, this was not statistically significant (P = 0.249, Wilcoxon Signed Rank). Hospital admissions improved from a median of 3 (IQR 4) in the year prior to BT to 1 (IQR 2) in the last year (Fig. 2), a difference which trended towards statistical significance (P = 0.059). Admission rates for individual subjects are shown in Fig. 3. The overall median exacerbation rate showed only a modest improvement from 5 (IQR 3)–4 (IQR 6) (P = 0.402). There was an increase in maintenance oral corticosteroid requirement from prior to BT, median 10 mg (IQR 30 mg), to 4 years post-BT, median 20 mg (IQR 25 mg) (P = 1.000). There was a small reduction in mean FEV1 from 1.68 l prior to BT to 1.46 l 4 years post-procedure however this was not statistically significant (P = 0.463) Fig. 4. There was no mortality among the group. Figure 1 View largeDownload slide Median Asthma Control Test (ACT) scores pre and post Bronchial Thermoplasty. Figure 1 View largeDownload slide Median Asthma Control Test (ACT) scores pre and post Bronchial Thermoplasty. Figure 2 View largeDownload slide Median yearly admission rate pre and post Bronchial Thermoplasty. Figure 2 View largeDownload slide Median yearly admission rate pre and post Bronchial Thermoplasty. Figure 3 View largeDownload slide Yearly admission rate per patient pre and post Bronchial Thermoplasty. Figure 3 View largeDownload slide Yearly admission rate per patient pre and post Bronchial Thermoplasty. Figure 4 View largeDownload slide Prebronchodilator FEV1 per patient pre and post Bronchial Thermoplasty. Figure 4 View largeDownload slide Prebronchodilator FEV1 per patient pre and post Bronchial Thermoplasty. Conclusions The function of ASM has been subject to debate for many years, multiple roles in normal function have been postulated including immunomodulation, extracellular matrix deposition and regulation of bronchomotor tone8 with some claiming it is a vestigial structure without an essential function.9 It has been shown that asthmatics have an increased volume of ASM compared with normal controls and those with fatal asthma have increased ASM cell hyperplasia when compared to subjects with non-fatal asthma.10 In severe asthma, the increased ASM contributes to bronchoconstriction, airway inflammation and airway remodelling. It is, therefore, reasonable to suggest that a reduction in ASM could potentially improve bronchoconstriction and airway remodelling leading to better asthma control. BT targets ASM by using thermal energy to reduce ASM mass and its contractility, all airways distal to the mainstream bronchi between 3 and 10 mm in diameter are treated except in the right middle lobe.11 The manufacturer advises against treatment of the right middle lobe due to the narrow diameter of the lobar bronchus and its acute take-off angle, characteristics which may promote atelectasis or difficulty in re-inflation if transient obstruction occurs as a result of procedure-related inflammation or oedema. Although bronchoconstriction occurs throughout the bronchial tree in asthma, and it is not certain what the relative contribution of central and peripheral airways to airflow obstruction is, the greatest source of resistance to airflow in the normal bronchial tree is in the conducting airways at about the fourth generation.12 Therefore it is likely that narrowing in this area would cause a greater effect to overall airflow obstruction and treating more central airways should have a therapeutic effect. Although our patient group is small, we have shown an enduring reduction in hospital admission rates after 4 years of follow-up which trends towards statistical significance. This translates into a significant benefit for our patient group with regard to quality of life and a reduction in healthcare costs associated with their asthma. The National Health Service in the United Kingdom estimates costs associated with an emergency admission at over €120013 while lost work days also carry a significant economic burden. Our initial study on these patients showed a significant improvement in ACT scores in this study we could not show a statistically significant improvement in ACT so persistence of efficacy was not demonstrated however the improvement did reach the MCID which is encouraging. While BT is included in GINA guidelines,4 it should be noted that caution is advised in selecting patients, and they note that longer-term follow-up is needed with regard to effectiveness and safety. They advise that BT is an option for patients whose asthma remains uncontrolled despite optimised therapeutic regimens and referral to an asthma specialty centre.4 Our patient group were all assessed in a severe asthma centre and underwent a minimum of 3 months of close supervision with maintenance medications prior to the procedure in order to ensure compliance with medications, only when optimised according to GINA guidelines did we proceed to thermoplasty. Reassuringly there was no significant drop in FEV1 in our patient group and no mortality. This is especially reassuring given that the original sham controlled study excluded patients with an FEV1 <60%5 whereas our group included patients with severe disease several of whom had FEV1 <60% and many were frequent exacerbators. This is a valuable contribution to our knowledge regarding safety of BT. This study adds to our experience of BT for the treatment of severe asthma. Our initial data from this group 1 year post-intervention showed a statistically significant improvement in the ACT scores and a reduction in hospital admissions which trended towards statistical significance. Here we have shown durability of effect of the treatment and safety of the procedure which is consistent with international data.7 BT warrants ongoing study as although it is an invasive, relatively costly intervention it provides therapeutic options in a population who are currently difficult to treat and alternative emerging asthma therapy also carry a significant financial burden. Further characterization of the asthma sub-phenotypes who are likely to exhibit the greatest clinical benefit from BT would be helpful in the management of severe asthma. Conflict of interest: None declared. References 1 Manning P, Shanahan E, O'Connor T, Elnazir B, Ni Chroinin M, Williams N, et al.   A multicentre programme in primary care to evaluate current asthma control among patients and examine barriers and facilitators to the implementation of evidence based GINA asthma guidelines in the Republic of Ireland (RoI). Ir J of Med Sci  2010; 179: S478. 2 Central Statistics Office. Report on Vital Statistics 2002 to 2010. Dublin, Stationary Office, 2010. 3 Weiss KB, Sullivan SD. The health economics of asthma and rhinitis. 1 Assessing the economic impact. J Allergy Clin Immunol  2001; 107: 3– 8. Google Scholar CrossRef Search ADS PubMed  4 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2017. www.gina.org (30 May 2017, date last accessed). 5 Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, et al.  ; AIR2 Trial Study Group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med  2010; 181: 116– 24. http://dx.doi.org/10.1164/rccm.200903-0354OC Google Scholar CrossRef Search ADS PubMed  6 Castro M, Rubin A, Laviolette M, Hanania NA, Armstrong B, Cox G; AIR2 Trial Study Group. Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma. Ann Allergy Asthma Immunol  2011; 107: 65– 7. Google Scholar CrossRef Search ADS PubMed  7 Watchorn DC, Sahadevan A, Egan JJ, Lane SJ. The efficacy of bronchial thermoplasty for severe persistent asthma: the first national experience. Ir Med J  2016; 109: 406. Google Scholar PubMed  8 Panettieri RA, Kotlikoff MI, Gerthoffer WT, Hershenson MB, Woodruff PG, Hall IP, et al.   Airway smooth muscle in bronchial tone, inflammation, and remodeling. Am J Respir Crit Care Med  2008; 177: 248– 52. Google Scholar CrossRef Search ADS PubMed  9 Mitzner W. Airway smooth muscle: the appendix of the lung. Am J Respir Crit Care Med  2004; 169: 787– 90. http://dx.doi.org/10.1164/rccm.200312-1636PP Google Scholar CrossRef Search ADS PubMed  10 Carroll N, Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis  1993; 147: 405– 10. http://dx.doi.org/10.1164/ajrccm/147.2.405 Google Scholar CrossRef Search ADS PubMed  11 Cox G, Miller J, McWilliams A, Fitzgerald J, Lam S. Bronchial thermoplasty for asthma. Am J Respir Crit Care Med  2006; 173: 965– 9. Google Scholar CrossRef Search ADS PubMed  12 Hogg JC. The pathology of asthma. APMIS  1997; 105: 735– 45. http://dx.doi.org/10.1111/j.1699-0463.1997.tb05079.x Google Scholar CrossRef Search ADS PubMed  13 National Health Service. Better for Less. https://www.networks.nhs.uk/nhs-networks/respiratory-leads/yorkshire-humber-respiratory-programme/documents/Better%20for%20Less%20-%20%20Asthma%20-Yorks%20-%20Humber.pdf (21 May 2017, date last accessed). © The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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QJM: An International Journal of MedicineOxford University Press

Published: Mar 1, 2018

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