COPD: Do more for your symptomatic COPD patients

On 13 and 17 October 2020, COPDAS organised a webinar on improving quality of life in symptomatic COPD patients, as part of OEP’s effort in supporting continuous medical education amongst healthcare professionals. The 2-hour virtual event was attended live by more than 100 healthcare practitioners over both days.

Chaired by Dr Perng Diahn Warng and Dr Tan Tze Lee, a global panel of pulmonary experts discussed the latest developments in COPD treatment approaches.

To commence the session, a hearty discussion took place between Singapore and Taiwan on the prevalence of COPD in both countries and the importance of early diagnosis in patients with COPD. With Dr Perng and Dr Tan’s warm and resounding welcome to kick-off on a high note, participants were captivated about the contents of the presentations.

The Novel, Fixed, Extra-Fine Triple Combination for COPD

by Prof Dave Singh

Increasing frequency and severity of COPD exacerbations are associated with higher risk of death.⁷ In other words, patients with more exacerbations and hospitalisations have worse prognosis. Hence, pharmacological treatment that reduces exacerbations would likely have a benefit on mortality rate.

COPD has a predominant small airway pathophysiology. Acute inflammatory cells increase in the small airways⁸ and small airways get destroyed⁹  as COPD progresses from stage 1 to 4. It is known that use of ICS is associated with increased risk of adverse events. As they are dose-related, limiting the dose of ICS use could reduce adverse events.

Extra-fine formulation of inhaled particles showed higher deposition in the small airways, enabling a more efficient drug delivery and a lower dose to limit adverse events. In a study comparing extra-fine beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide [BDP/FF/GB] pressurized metered dose inhaler (pMDI) and non-extrafine fluticasone furoate/vilanterol/umeclidinium [FluF/VI/UMEC] dry powder inhaler (DPI), BDP/FF/GB had higher peripheral deposition of all three components (ICS, LABA, LAMA) compared with FluF/VI/UMEC, which is consistent with the extra-fine particle size formulation of BDP/FF/GB.¹⁰   

A randomised, parallel-group, double-blind study (TRILOGY) showed a significant 23% reduction in moderate-to-severe COPD exacerbations using BDP/FF/GB compared with BDP/FF.¹¹  

A similar study (TRINITY) was done to compare BDP/FF/GB with tiotropium, and BDP/FF plus tiotropium.¹²  BDP/FF/GB significantly reduced the rate of moderate-to-severe COPD exacerbations by 20% compared with tiotropium alone, and was similar to BDP/FF plus tiotropium but offers the simplicity of using one inhaler.¹²  Patients with higher eosinophil count (≥ 2%) also benefited more from fixed triple therapy with 30% reduction in moderate-to-severe exacerbation rate over tiotropium.¹²

The TRIBUTE study compared single-inhaler triple therapy combination of BDP/FF/GB with the single-inhaler dual bronchodilator combination of indacaterol and glycopyrronium (IND/GLY).¹³  In patients with symptomatic COPD, severe or very severe airflow limitation, and an exacerbation history despite maintenance therapy, extra-fine BDP/FF/GB significantly reduced the rate of moderate-to-severe exacerbations by 15% compared with IND/GLY, without increasing the risk of pneumonia.¹³

In summary, the robust clinical trial evidence that single-inhaler extra-fine BDP/FF/GB (Trimbow®) reduces exacerbations compared to double combination treatments and LAMA monotherapy cements triple therapy positioning as an escalation step in COPD management pathways.¹⁴

Blood eosinophil counts are increasingly used to support clinical decision making regarding ICS use. GOLD recommendations focus on integrating clinical assessment with eosinophil counts to optimize treatment choice in the prevention of exacerbations.1 Eosinophilic COPD patients appear to have a wider profile of type 2 inflammation, which provides an explanation for the increasing benefit of ICS at higher blood eosinophil counts.¹⁵  

COPD 2020 Guidelines: Good as GOLD?

by Dr Ong Kian Chung

GOLD 2020 recommended initial pharmacological approach of COPD to be based on assessment of symptoms, mainly dyspnea, and frequency of exacerbations for treatment-naive patients.¹

Triple therapy combinations of LABA/LAMA/ICS have reported reduced mortality in comparison to LAMA, LABA/LAMA or LABA/ICS.^2,3  Recent studies target patient populations with increased respiratory symptoms and a prior history of frequent and/or severe exacerbations.¹  The effect of inhaled corticosteroid (ICS)-containing treatments on survival in symptomatic severe and very severe COPD patients seem optimistic, particularly considering that combination therapy, especially triple therapy, is almost invariably required in these patients to improve symptoms or quality of life, or to reduce exacerbations and hospitalisations.³ Consideration to de-escalate ICS after achieving respiratory stability should be done with caution in this group of patients.¹

COPD patients view symptoms of breathlessness and limitation of physical activities as the worst aspects of their condition.⁴ Dyspnea is not solely attributed to airway limitation. Patients who experience dyspnea goes through a downward spiral of chronic inactivity that leads to reduction in exercise tolerance and physical deconditioning, which further worsens dyspnea and quality of life.⁵ Hence, targeting contributory factors of physical deconditioning is essential in addition to improving airway obstruction to alleviate dyspnea in COPD patients. Exercise limitation, while closely associated with dyspnea, is shown to be the strongest predictor of all-cause mortality in COPD patients.⁶

If patients are persistently dyspneic despite reaching maximum doses of long-acting bronchodilators, other factors for consideration include:

1. Medication adherence with dosing regimen and inhaler techniques
2. Small airway dysfunction
   Drug delivery to lower respiratory tract and lungs require smaller inhaled particle size; fine (2-5 µm) or extra-fine (< 2 µm), with more peripheral deposition using extra-fine particles.¹
3. Non-pharmacological interventions
   Exercise training has been identified as a major component of pulmonary rehabilitation which is the most effective therapeutic strategy to improve dyspnea, health status and exercise tolerance. According to GOLD Report 2020, non-pharmacological treatment is complementary to pharmacological treatment and should form part of the comprehensive management of COPD.¹

For persistently symptomatic COPD patients, treatment strategy that targets to optimise both lung function and exercise tolerance should be considered.

Case Study: Symptomatic COPD Patients – How to do more for them

by Dr Alvin Ng

Dr Ng used case studies to illustrate successful stories of his patients who showed clinical improvements with the use of extra-fine particle combination therapy.

In the first case, a patient recorded an exhaled nitric oxide (FeNO) level of 74 ppb and FEV1 of 29% at first visit. Dr Ng started the patient on extra-fine Foster® (BDP/FF) NEXThaler, and patient’s FEV1 subsequently improved to 65% and no longer experience symptoms of dyspnea.

Another patient who presented with emphysema had worsening cough when he started on Spiolto® (tiotropium/olodaterol). Patient’s FEV1 was 35% with FeNO level recorded at 132 ppb. Dr Ng switched patient’s therapy to extra-fine Foster® (BDP/FF) pMDI and patient’s FeNO subsequently decreased to 44 ppb.

NEXThaler is the first DPI delivering extra-fine particles. The unique characteristic mainly depends on the use of specific extra-fine formulation powder and a highly innovative release and deaggregation system. DPIs differ from pMDIs in that they are breath-actuated and do not require patient breath-dose coordination.

As patient inhales into the NEXThaler, inhaled air enters the cyclone chamber and causes high turbulence intensity and particle-wall collisions, resulting in efficient deaggregation and release of drug particles from the carriers. NEXThaler utilises 3 types of feedback mechanism when sufficient flow rate is reached; a click can be heard when a dose is successfully activated, dose counter to display remaining doses, and a distinctive taste (lactose).

What’s next in store?

• Check out the full document with figures included:

Do more for your symptomatic COPD patients

• See the full video recording on our Medical Channel Asia’s YouTube channel:

[embedyt] https://www.youtube.com/watch?v=LvwF3dbBDdk[/embedyt]

References:

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2020 Report). Available at: https://goldcopd.org/ (Accessed: October 2020).
2. Lipson DA, Barnhart F, Brealey N, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. New England Journal of Medicine. 2018;378(18):1671-1680.
3. Vestbo J, Fabbri L, Papi A, et al. Inhaled corticosteroid containing combinations and mortality in COPD. European Respiratory Journal. 2018;52(6):1801230.
4. Svedsater H, Roberts J, Patel C, et al. Life Impact and Treatment Preferences of Individuals with Asthma and Chronic Obstructive Pulmonary Disease: Results from Qualitative Interviews and Focus Groups. Advances in Therapy. 2017;34(6):1466-1481.
5. Decramer M. Tiotropium as essential maintenance therapy in COPD. European Respiratory Review. 2006;15:51-57.
6. Waschki B, Kirsten A, Holz O, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest. 2011;140(2):331-342.
7. Rothnie KJ, Müllerová H, Smeeth L, Quint JK. Natural History of Chronic Obstructive Pulmonary Disease Exacerbations in a General Practice-based Population with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2018;198(4):464-471.
8. Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. New England Journal of Medicine. 2004;350(26):2645-53.
9. McDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med. 2011;365(17):1567-1575.
10. Topole E, Usmani O, Mignot B, et al. Lung deposition of extrafine vs non-extrafine triple therapies in patients with COPD using Functional Respiratory Imaging (FRI). European Respiratory Journal. 2019;54(63):3167
11. Singh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016;388(10048):963-973.
12. Vestbo J, Papi A, Corradi M, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet. 2017;389(10082):1919-1929.
13. Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018;391(10125):1076-1084.
14. Singh D. Single inhaler triple therapy with extrafine beclomethasone, formoterol, and glycopyrronium for the treatment of chronic obstructive pulmonary disease. Expert Opinion on Pharmacotherapy. 2018;19(11):1279-1287.
15. Singh D. Blood Eosinophil Counts in Chronic Obstructive Pulmonary Disease: A Biomarker of Inhaled Corticosteroid Effects. Tuberculosis and Respiratory Diseases. 2020;83:185-194.