COPD inhaler therapy: A path to success

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doi:doi: 10.12788/jfp.0469

Applied Evidence

COPD inhaler therapy: A path to success

J Fam Pract. 2022 September;71(7):280-289 | doi: 10.12788/jfp.0469

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References

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7. Navaie M, Dembek C, Cho-Reyes S, et al. Device use errors with soft mist inhalers: a global systematic literature review and meta-analysis. Chron Respir Dis. 2020;17:1479973119901234. doi:10.1177/1479973119901234

8. Sharma G, Mahler DA, Mayorga VM, et al. Prevalence of low peak inspiratory flow rate at discharge in patients hospitalized for COPD exacerbation. Chronic Obstr Pulm Dis. 2017;4:217-224. doi: 10.15326/jcopdf.4.3.2017.0183

9. Chen SY, Huang CK, Peng HC, et al. Peak-inspiratory-flow-rate guided inhalation therapy reduce severe exacerbation of COPD. Front Pharmacol. 2021;12:704316. doi: 10.3389/fphar.2021.704316

10. Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011;105:930-938. doi:10.1016/j.rmed.2011.01.005

11. Fathima M, Bawa Z, Mitchell B, et al. COPD management in community pharmacy results in improved inhaler use, immunization rate, COPD action plan ownership, COPD knowledge, and reductions in exacerbation rates. Int J Chron Obstruct Pulmon Dis. 2021;16:519-533. doi: 10.2147/COPD.S288792

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13. Brunetti L, Poiani G, Dhanaliwala F, et al. Clinical outcomes and treatment cost comparison of levalbuterol versus albuterol in hospitalized adults with chronic obstructive pulmonary disease or asthma. Am J Health Syst Pharm. 2015;72:1026-1035. doi:10.2146/ajhp140551

14. Brown CD, McCrory DC, White J. Inhaled short-acting beta2-agonists versus ipratropium for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2001;2001:CD002984. doi: 10.1002/14651858.CD002984

15. Kew KM, Mavergames C, Walters JAE. Long-acting beta₂-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013;(10):CD010177. doi: 10.1002/14651858.CD010177.pub2

16. Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;2014:CD009285. doi:10.1002/14651858.CD009285.pub3

17. Chong J, Karner C, Poole P. Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;2012:CD009157. doi:10.1002/14651858.CD009157.pub2

18. Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta₂-agonist in one inhaler versus long-acting beta₂-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;2012:CD006829. doi: 10.1002/14651858.CD006829.pub2

19. Yun JH, Lamb A, Chase R, et al; COPDGene and ECLIPSE Investigators. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141:2037-2047.e10. doi:10.1016/j.jaci.2018.04.010

20. Agusti A, Fabbri LM, Singh D, et al. Inhaled corticosteroids in COPD: friend or foe? Eur Respir J. 2018;52:1801219. doi:10.1183/13993003.01219-2018

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22. Calverley PMA, Anderson JA, Celli B, et al; TORCH Investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775-789. doi:10.1056/NEJMoa063070

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25. Horita N, Goto A, Shibata Y, et al. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2017;2:CD012066. doi:10.1002/14651858.CD012066.pub2

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LABA + LAMA. In a trial of patients with moderate-to-severe COPD, combining a LABA and a LAMA did not reduce the risk of exacerbations or hospitalizations, compared to LABA or LAMA monotherapy, but did improve subjects’ reported daily symptoms and quality of life scores (using the St. George’s Respiratory Questionnaire^b; NNT = 14 [LAMA monotherapy] and NNT = 9 [LABA monotherapy], both in a 3 to 12–month period).²⁴ However, another study that looked at patients with moderate-to-severe COPD found that combining a LABA and a LAMA led to fewer exacerbations (NNT = 22, to prevent 1 exacerbation in a 3 to 12–month period) and a lower risk of pneumonia (NNT = 93, to prevent 1 case of pneumonia in a 3 to 12–month period) than LABA + ICS.²⁵

LABA + ICS. This dual therapy is falling out of favor, compared to treatment with LABA + LAMA, because LABA + ICS formulations are less effective at reducing exacerbations and increase the risk of pneumonia in patients with moderate-to-severe COPD.^1,25 However, LABA + ICS therapy still has a role in a subset of patients with COPD (discussed in the section on ICS). A LABA combined with an ICS does reduce exacerbations in patients with severe COPD (NNT = 22, to prevent 1 exacerbation per year).¹⁸ Expect that the reported rates of candidiasis, hoarseness, and pneumonia associated with an ICS will be similar with LABA + ICS.¹⁸

LABA + LAMA + ICS. These are the newest combination inhaled agents approved for clinical use. It is recommended that escalation to such triple therapy be reserved for patients with persistent dyspnea on LAMA + LABA therapy and who have the factors (previously described) that suggest benefit from adding an ICS.¹ Several clinical trials have provided guidance:

In the 2018 TRIBUTE trial,²⁶ beclometasone (ICS) + formoterol (LABA) + glycopyrronium (LAMA) ^c outperformed indacaterol (LABA) + glycopyrronium for preventing moderate-to-severe exacerbations (NNT = 11, to prevent 1 exacerbation per year) in patients with symptomatic COPD who have severe or very severe airflow resistance and a history of a moderate-to-severe exacerbation during the previous year.
In the 2017 TRINITY trial,²⁷ beclometasone + formoterol + glycopyrronium^c outperformed tiotropium (LAMA) in preventing moderate-to-severe exacerbations (NNT = 9, to prevent 1 exacerbation per year) in patients with an FEV₁ < 50% and a history of ≥ 1 moderate-to-severe exacerbation during the previous year.
In the 2020 ETHOS trial,²⁸ budesonide + formoterol + glycopyrronium (approved by the FDA in 2020 under the brand name Breztri) outperformed both glycopyrrolate + formoterol (LABA) and budesonide (ICS) + formoterol in preventing moderate-to-severe exacerbations (NNT = 56 and 34, respectively, to prevent 1 exacerbation per year) in patients with moderate-to-severe COPD who had a history of ≥ 1 exacerbation in the previous year. Additionally, higher-dose budesonide + formoterol + glycopyrronium reduced 1-year mortality to a modest degree compared to glycopyrrolate + formoterol (NNT = 100, to prevent 1 death in a 12-month period).
A 2016 Cochrane review that compared tiotropium + LABA + ICS to tiotropium monotherapy²⁹ showed improvement in FEV₁ and patient-reported symptoms and quality of life scores. However, the review showed no difference in exacerbations or hospitalizations over a 1-year period.

Mitigating environmental exposures that affect inhaler medication efficacy

Tobacco smoke. Emphasizing smoking cessation is highly relevant in patients who are still smoking. Smoking impedes the efficacy of ICSs in reducing exacerbations of COPD.³⁰ Along with improved lung function, former smokers with COPD experience fewer exacerbations (NNT = 73, to prevent 1 exacerbation in a 4-year period for all former smokers; NNT = 33, to do so for smokers who quit > 10 years ago).^31,32

The continuous use of shortacting betaagonist nebulizer therapy can increase the risk of disease transmission through the generation of droplets.

A 2005 Veterans Health Administration study showed reduced mortality in smokers who were enrolled in a 10-week smoking cessation program, had access to nicotine replacement therapy, and received strong physician messaging.³³ Despite a 20% to 25% quit rate, the NNT was 56 to prevent 1 death in 14.5 years across the entire group. It is worth having patients take advantage of this 3-pronged approach if it is available in your community or health system.

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