Bronchial thermoplasty for moderate or severe persistent asthma in adults

  • Review
  • Intervention

Authors

  • Alfons Torrego,

    Corresponding author
    1. Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomédica Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona Respiratory Network (BRN), Pulmonology Department, Barcelona, Spain
    • Alfons Torrego, Pulmonology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomédica Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona Respiratory Network (BRN), Sant Antoni Maria Claret 167, Barcelona, 08025, Spain. atorrego@santpau.cat.

    Search for more papers by this author
  • Ivan Solà,

    1. CIBER Epidemiología y Salud Pública (CIBERESP), Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Catalunya, Spain
    Search for more papers by this author
  • Ana Maria Munoz,

    1. Hospital de la Santa Creu i Sant Pau, Unit of Bronchoscopy, Respiratory Department, Barcelona, Spain
    Search for more papers by this author
  • Marta Roqué i Figuls,

    1. CIBER Epidemiología y Salud Pública (CIBERESP), Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Catalunya, Spain
    Search for more papers by this author
  • Juan Jose Yepes-Nuñez,

    1. McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton, Ontario, Canada
    2. University of Antioquia, Colombia, Group of Clinical and Experimental Allergy, Medellín, Antioquia, Colombia
    Search for more papers by this author
  • Pablo Alonso-Coello,

    1. Biomedical Research Institute Sant Pau (IIB Sant Pau), Iberoamerican Cochrane Centre, Barcelona, Catalunya, Spain
    Search for more papers by this author
  • Vicente Plaza

    1. Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomédica Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona Respiratory Network (BRN), Pulmonology Department, Barcelona, Spain
    Search for more papers by this author

Abstract

Background

Bronchial thermoplasty is a procedure that consists of the delivery of controlled radiofrequency-generated heat via a catheter inserted into the bronchial tree of the lungs through a flexible bronchoscope. It has been suggested that bronchial thermoplasty works by reducing airway smooth muscle, thereby reducing the ability of the smooth muscle to bronchoconstrict. This treatment could then reduce asthma symptoms and exacerbations, resulting in improved asthma control and quality of life.

Objectives

To determine the efficacy and safety of bronchial thermoplasty in adults with bronchial asthma.

Search methods

We searched the Cochrane Airways Group Specialised Register of Trials (CAGR) up to January 2014.

Selection criteria

We included randomised controlled clinical trials that compared bronchial thermoplasty versus any active control in adults with moderate or severe persistent asthma. Our primary outcomes were quality of life, asthma exacerbations and adverse events.

Data collection and analysis

Two review authors independently extracted data and assessed risk of bias.

Main results

We included three trials (429 participants) with differences regarding their design (two trials compared bronchial thermoplasty vs medical management and the other compared bronchial thermoplasty vs a sham intervention) and participant characteristics; one of the studies included participants with more symptomatic asthma compared with the others.

The pooled analysis showed improvement in quality of life at 12 months in participants who received bronchial thermoplasty that did not reach the threshold for clinical significance (3 trials, 429 participants; mean difference (MD) in Asthma Quality of Life Questionnaire (AQLQ) scores 0.28, 95% confidence interval (CI) 0.07 to 0.50; moderate-quality evidence). Measures of symptom control showed no significant differences (3 trials, 429 participants; MD in Asthma Control Questionnaire (ACQ) scores -0.15, 95% CI -0.40 to 0.10; moderate-quality evidence). The risk of bias for these outcomes was high because two of the studies did not have a sham intervention for the control group.

The results from two trials showed a lower rate of exacerbation after 12 months of treatment for participants who underwent bronchial thermoplasty. The trial with sham intervention showed a significant reduction in the proportion of participants visiting the emergency department for respiratory symptoms, from 15.3% on sham treatment to 8.4% over 12 months following thermoplasty. The trials showed no significant improvement in pulmonary function parameters (with the exception of a greater increase in morning peak expiratory flow (PEF) in one trial). Treated participants who underwent bronchial thermoplasty had a greater risk of hospitalisation for respiratory adverse events during the treatment period (3 trials, 429 participants; risk ratio 3.50, 95% CI 1.26 to 9.68; high-quality evidence), which represents an absolute increase from 2% to 8% (95% CI 3% to 23%) over the treatment period. This means that six of 100 participants treated with thermoplasty (95% CI 1 to 21) would require an additional hospitalisation over the treatment period. No significant difference in the risk of hospitalisation was noted at the end of the treatment period.

Bronchial thermoplasty was associated with an increase in respiratory adverse events, mainly during the treatment period. Most of these events were mild or moderate, appeared in the 24-hour post-treatment period, and were resolved within a week.

Authors' conclusions

Bronchial thermoplasty for patients with moderate to severe asthma provides a modest clinical benefit in quality of life and lower rates of asthma exacerbation, but no significant difference in asthma control scores. The quality of life findings are at risk of bias, as the main benefits were seen in the two studies that did not include a sham treatment arm. This procedure increases the risk of adverse events during treatment but has a reasonable safety profile after completion of the bronchoscopies. The overall quality of evidence regarding this procedure is moderate. For clinical practice, it would be advisable to collect data from patients systematically in independent clinical registries. Further research should provide better understanding of the mechanisms of action of bronchial thermoplasty, as well as its effect in different asthma phenotypes or in patients with worse lung function.

摘要

以支氣管熱整形術治療中度或重度持續性氣喘成人患者

背景

支氣管熱整形術 (bronchial thermoplasty) 是一種程序,經由有彈性的支氣管鏡,將導管插入肺部的支氣管樹,在控制下遞送射頻產生的熱。支氣管熱整型術可減少氣管的平滑肌,藉以降低平滑肌導致支氣管收縮的能力。因此這種治療可減輕氣喘的症狀和發作(exacerbation),進而改善氣喘控制和生活品質。

目的

判斷支氣管熱整型術對支氣管氣喘 (bronchial asthma) 成人患者的療效和安全性。

搜尋策略

我們搜尋截至2014年1月為止的考科藍氣管群組試驗專業註冊(Cochrane Airways Group Specialised Register of Trials, CAGR)。

選擇標準

我們納入隨機對照臨床試驗,研究對象為罹患中度或重度持續性氣喘 (persistent asthma) 的成人患者,採用的治療為支氣管熱整型術與任何有效控制。主要結果為生活品質、氣喘發作和不良事件。

資料收集與分析

由2位文獻回顧作者獨立進行資料萃取,並評估偏差風險。

主要結果

我們納入3篇試驗 (429名受試者),這些試驗的設計 (其中2篇試驗比較支氣管熱整型術和內科治療,另1篇試驗則比較支氣管熱整型術和虛假介入 [sham intervention]) 和受試者特性有所不同,其中1篇試驗所收錄的受試者,氣喘症狀比其他2篇試驗嚴重。

匯集分析結果顯示,於第12個月時,接受支氣管熱整型術的受試者生活品質獲得改善,但並未達到具臨床意義的閾值 (3篇試驗,429名受試者,氣喘生活品質問卷[Asthma Quality of Life Questionnaire, AQLQ] 分數的平均差 [mean difference, MD] 為0.28,95%信賴區間 [confidence interval, CI] 為 0.07至0.50;證據品質中等)。症狀控制的測量結果並無顯著差異 (3篇試驗,429名受試者,氣喘控制問卷 [Asthma Control Questionnaire, ACQ] 分數MD為-0.15,95% CI為 -0.40至0.10;證據品質中等)。上述結果的偏差風險很高,因為其中2篇試驗並未建立使用虛假介入的對照組。

有2篇試驗的結果顯示,接受支氣管熱整型術的患者,於治療後12個月的氣喘發作發生率較低。設有虛假介入對照組的試驗結果則顯示,在接受治療後12個月,熱整型術治療組因呼吸症狀而到急診就醫的患者比例為8.4%,顯著低於虛假治療組患者 (15.3%)。些試驗顯示肺功能參數並無顯著改善 (但有1篇試驗其晨間尖峰呼氣流速[peak expiratory flow, PEF] 大幅增加的情況除外)。治療期間,支氣管熱整型術組患者,因呼吸不良事件而住院的風險較高 (3篇試驗,429名受試者;風險比為3.50, 95% CI為1.26至9.68),表示治療期間的絕對風險自2%增加至8% (95% CI為3%至23%)。亦即在治療期間,熱整型術治療組患者中有6%的人 (95% CI為1至21),需要額外住院治療。治療期結束時的住院風險並無顯著差異。

支氣管熱整型術可能導致呼吸道不良事件增加,主要發生於治療期間。大部分不良事件為輕度或中度,於治療後24小時內出現,並在1週內消除。

作者結論

支氣管熱整型術對中度至重度氣喘患者具有中度的臨床療效,可改善生活品質並降低氣喘發作的發生率,但對氣喘控制分數並無顯著影響。生活品質的測量結果具有偏差風險,因為2篇出現主要效益的試驗,並未建立虛假治療組。此項程序會使治療期間的不良事件風險增加,但支氣管鏡檢查完成後,則具有適當的安全性。此項程序的整體證據品質為中等。至於臨床實務,建議可系統性收集來自獨立臨床註冊的患者資料。未來的研究應朝向深入瞭解支氣管熱整型術的作用機轉,以及對各種氣喘表現型或肺功能更差之患者的療效。

譯註


翻譯者:臺北醫學大學實證醫學研究中心。
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

Plain language summary

Bronchial thermoplasty for people with asthma

Review question

We reviewed the effects of bronchial thermoplasty in people with asthma.

Background

Asthma is a chronic condition in which people experience symptoms of breathlessness, wheezing, coughing and chest tightness due to airway inflammation and airway muscle contraction. With inhaled treatments, including bronchodilators (drugs that relax airway muscle and so open up the airways) and steroids (which treat underlying inflammation in the lungs), symptoms usually can be controlled. However, for some people, asthma cannot be adequately controlled with these drugs, either because they are truly resistant or because they do not take them.

The muscle in the airways of the lungs is thicker in people with asthma than in people who do not have asthma. During asthma attacks, these muscles tighten, making it hard to breathe.

Bronchial thermoplasty is a relatively new procedure that reduces the amount of muscle bulk in the airways of the lungs. A long flexible tube, called a bronchoscope, is passed down into the lung under direct observation, and the walls of specific areas of the lungs are heated to 65 degrees Celsius. This causes some of the muscle to break up, making it harder for the muscles to tighten.

Generally, three sessions of treatment are given.

Study characteristics

We found three trials comparing groups of adults treated with bronchial thermoplasty versus adults who received standard medical treatment or a "sham" (simulated) bronchial thermoplasty treatment.

Key results

These studies showed moderate improvement only in quality of life of patients treated with bronchial thermoplasty and in the number of asthma attacks (exacerbations) that they experienced. In addition, patients treated with this procedure had more respiratory problems than patients who received the alternative intervention during the period when they were undergoing treatment, resulting in increased risk of hospitalisation due to a respiratory symptom during this phase, but not afterward.

Quality of evidence

Confidence in the results of this review is moderate because two of the studies had no sham intervention and there were differences regarding the characteristics of patients and the comparisons performed. More studies should be conducted to determine whether the observed effect and safety of bronchial thermoplasty are durable over the long term, and to identify whether particular patients can be identified who could benefit most.

This plain language summary is current as of January 2014.

淺顯易懂的口語結論

以支氣管熱整型術治療氣喘患者

回顧問題

我們回顧支氣管熱整型術對氣喘患者的療效。

背景

氣喘是一種慢性疾病,患者會因為氣管發炎和氣管肌肉收縮,而出現呼吸困難、喘鳴、咳嗽和胸悶等症狀。使用吸入劑治療,包括支氣管擴張劑 (可使氣管肌肉放鬆,進而打開呼吸道的藥物) 和類固醇,症狀通常可以獲得控制。不過部分患者無法利用這些藥物適當控制氣喘,無論是對藥物確實產生抗性或沒有使用藥物。

氣喘患者肺臟的呼吸道內部肌肉,比非氣喘患者厚。在氣喘發作時,氣管的肌肉會收縮,導致患者呼吸困難。

支氣管熱整型術是一種相當新的程序,可減少肺臟呼吸道內的肌肉體積。醫師會將1條名為支氣管鏡的彈性長管,在直接觀察下穿過氣管往下進入肺部,將肺臟特定部位的管壁加熱至攝氏65度,使部分肌肉分解,讓氣管的肌肉較不容易收縮。

一般而言,這項治療需要進行3個療程。

試驗特色

我們找到3篇試驗,比較支氣管熱整型術和標準內科治療,或「虛假」(假裝) 的支氣管熱整型術治療。

重要結果

這些試驗顯示,接受支氣管熱整型術治療的患者,只有生活品質和氣喘發作 (惡化) 次數出現中度改善。此外在治療期間,接受此項程序的患者,比接受其他介入的患者發生更多呼吸道的問題,所以在這個階段患者因呼吸症狀而住院的風險增高,不過治療結束後就不再有此種現象。

證據品質

本文獻回顧結果的可靠度中等,因為其中2篇試驗並未建立採用虛假介入的對照組,而且這些試驗所收錄的患者特性和比較方式也不相同。必須進行更多試驗,才能判斷支氣管熱整型術的療效和安全性是否可長期持續,並確認是否能找出最能因支氣管熱整型術獲益的特定患者。

截至2014年1月為止,這份一般語言總結仍然通用。

譯註


翻譯者:臺北醫學大學實證醫學研究中心。
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。