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The role of tiotropium in COPD

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The ABCD Assessment tool has been updated in the recent guidelines – the number provides information regarding airflow limitation (spirometry grading 1-4) and the letter provides information regarding symptom burden and risk of exacerbations which is used to guide therapy in COPD patients. The mainstay of COPD treatment is inhaled long-acting maintenance therapy with long-acting muscarinic antagonists (LAMAs) and/or long-acting 2-agonists (LABAs), either alone or in combination with inhaled corticosteroids (ICS).2 

GOLD Group B: LABA or LAMA?  

LAMA or LABA monotherapy is recommended as the initial treatment for COPD patients in group B (figure 2).1 There is strong evidence that LAMAs have a greater effect on exacerbation reduction in and fewer side effects compared with LABAs.1,4,5,6 Tiotropium bromide is safe and efficacious as a long-term, once daily LAMA.6 Treatment trials in COPD show a greater benefit in symptom control and lung function obtained from tiotropium compared with either short-acting anticholinergics (ipratropium) or LABAs.7 In most comparative studies of tiotropium and placebo, ipratropium, or salmeterol, tiotropium provided significant beneficial effects on lung function, including improvements in FEV1 and FVC.6 No other LAMA has been proven superior to tiotropium, making it an optimal LAMA as monotherapy.6 

GOLD GROUP C AND D:  BENEFITS OF TIOTROPIUM  

The prevention of acute exacerbations of COPD has been listed as a cardinal goal for patients who have COPD of any grade of severity.8 The prolonged and persistent bronchodilation achieved with tiotropium may reduce COPD exacerbations and COPD-related hospitalisation rates.1,9  Therefore, tiotropium monotherapy is particularly beneficial in patient groups C and D who are at a high risk of exacerbations.10 Escalation to combination therapy is indicated when exacerbations are persistent, and as an alternative choice in patients whose symptoms are more severe.10 

MAINTENANCE AND PULMONARY REHABILITATION 

In a recent interview, Prof Richard Casaburi, an expert on Pulmonary Rehabilitation from the UCLA School of Medicine, made the following comments – “Dynamic hyperinflation at a given level of exercise can be reduced in one of two ways: provide more time for exhalation or speed the rate of exhalation. Rehabilitative exercise does the former and bronchodilators the latter. It has been well shown that these approaches to reduce dynamic hyperinflation are additive, so it is to be expected that optimal bronchodilation will amplify the effectiveness of rehabilitative exercise.”11 

Tiotropium has been associated with significant improvement in exercise tolerance in COPD patients GOLD groups 2-4 .12 It improves the effectiveness of  pulmonary rehabilitation by significantly reduced dyspnoea, the need for ‘as needed’ short acting B2 agonist use and lung hyperinflation, resulting in improvement in exertional dyspnoea, exercise endurance and health-related quality of life.1,6,8  Therefore, long-term tiotropium maintenance therapy combined with pulmonary rehabilitation and exercise training should be considered part of the integrated management in patients with COPD.1  

REFERENCES:  

  1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (2022 Report) [Internet]. 2022 p. 48, p. 51, p 92. Available from: https://goldcopd.org/wp-content/uploads/2021/12/GOLD-REPORT-2022-v1.1-22Nov2021_WMV.pdf   
  2.  Quint J, Montonen J, Singh D, Wachtel H, Attick S, Palli S, Frazer M, Willey V, Giessel G. New insights into the optimal management of COPD: extracts from CHEST 2021 annual meeting (October 17-20, 2021). Expert Rev Respir Med. 2022 Apr;16(4):485-493. doi: 10.1080/17476348.2022.2056022. Epub 2022 Apr 13. PMID: 35325585. 
  3.  https://bestpractice.bmj.com/topics/en-gb/7/images-and-videos 
  4.  Wedzicha JA, Calverley PMA, Albert RK, Anzueto A, Criner GJ, Hurst JR, Miravitlles M, Papi A, Rabe KF, Rigau D, Sliwinski P, Tonia T, Vestbo J, Wilson KC, Krishnan JA. Prevention of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017 Sep 9;50(3):1602265. doi: 10.1183/13993003.02265-2016. PMID: 28889106. 
  5.  https://www.knowledgehub.org.za/system/files/elibdownloads/2020-08/lama_%20copd%20review-n_december%202017.pdf 
  6.  Anzueto A, Miravitlles M. Tiotropium in chronic obstructive pulmonary disease – a review of clinical. Development. Respiratory Research (2020) 21:199 
  7.  Cheyne L, Irvin-Sellers MJ, White J. Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013 Sep 16;(9):CD009552. doi: 10.1002/14651858.CD009552.pub2. Update in: Cochrane Database Syst Rev. 2015;(9):CD009552. PMID: 24043433. 
  8.  Zhou Y, Zhong NS, Li X, Chen S, Zheng J, Zhao D, Yao W, Zhi R, Wei L, He B, Zhang X, Yang C, Li Y, Li F, Du J, Gui J, Hu B, Bai C, Huang P, Chen G, Xu Y, Wang C, Liang B, Li Y, Hu G, Tan H, Ye X, Ma X, Chen Y, Hu X, Tian J, Zhu X, Shi Z, Du X, Li M, Liu S, Yu R, Zhao J, Ma Q, Xie C, Li X, Chen T, Lin Y, Zeng L, Ye C, Ye W, Luo X, Zeng L, Yu S, Guan WJ, Ran P. Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Sep 07;377(10):923-935. [PubMed] 
  9.  Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008 Oct 9;359(15):1543-54. doi: 10.1056/NEJMoa0805800. Epub 2008 Oct 5. PMID: 18836213. 
  10.  Chen CY, Chen WC, Huang CH, Hsiang YP, Sheu CC, Chen YC, Lin MC, Chu KA, Lee CH, Wei YF. LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis. Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620937194. doi: 10.1177/1753466620937194. PMID: 32643547; PMCID: PMC7350046 
  11.  Troosters T, Casaburi R. Interview with Prof. Dr Richard Casaburi, Presidential Awardee 2020. Breathe (Sheff). 2020 Dec;16(4):200249. doi: 10.1183/20734735.0249-2020. PMID: 33447296; PMCID: PMC7792851. 
  12.  Casaburi R, Maltais F, Porszasz J, Albers F, Deng Q, Iqbal A, Paden HA, O'Donnell DE; 205.440 Investigators. Effects of tiotropium on hyperinflation and treadmill exercise tolerance in mild to moderate chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014 Nov;11(9):1351-61. doi: 10.1513/AnnalsATS.201404-174OC. PMID: 25289942. 

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