Treating Breathlessness, Improving QOL in Patients With COPD

Dual bronchodilators have been shown to broadly improve symptoms and quality of life (QOL) in patients with chronic obstructive pulmonary disease (COPD).

In patients with chronic obstructive pulmonary disease (COPD), dyspnea, or breathlessness, can greatly impact their life, but they learn to live with it and adapt rather than seek treatment for it, according to panelists during a discussion at the European Respiratory Society International Congress 2021.

Many patients and clinicians fixate on exacerbations for patients with COPD, but the reality is the more mundane, day-to-day symptoms, such as dyspnea, which affect quality and quantity of life are much more common, explained Sarah Jarvis, MBE, FRCGP, general practitioner in the United Kingdom and a broadcaster with the BBC, during the discussion.

Providers need to be more proactive finding out the activity levels of their patients with COPD, said MeiLan Han, MD, professor of internal medicine at the University of Michigan. Often these patients, even when they have breathlessness, don’t bring it up with their providers because they have learned how to adapt and live with it.

Research has shown that a majority (73%) of patients experience breathlessness, despite being on maintenance therapy.1 Furthermore, 64% experience phlegm and 59% experience cough. In addition, symptoms don’t only appear in patients with very severe disease, as 84% of patients with mild disease and 89% of patients with moderate disease also experience symptoms.2 The findings show that providers can’t assume patients don’t need treatment or experience symptoms, Han said.

When thinking about how COPD impacts what gives people pleasure in life, such as walking the dog, playing with grandchildren, or just going to the store, “that symptom of breathlessness and the limitation that leads to, we really have to be better at identifying it and addressing it,” said John R. Hurst, BSc, MBChB, MRCP, PhD, FRCP, FHEA, professor of respiratory medicine at University College London.

He recommends asking these patients about what they’ve had to change or what they can no longer enjoy in life. Asking about symptoms is important but doesn’t always provide the answers physicians need to treat patients with COPD.

“…if you really want to understand the impact that [breathlessness] has on the patient, ask them what’s changed in their life and what adaptations they’ve had to do to make that change,” Hurst said.

There is a fixation on exacerbations, but more than half of patients don’t experience a single exacerbation in a year and only 22% have 2 or more exacerbations in a year.3 Breathlessness is a big concern because it affects not only the things they can do, but their activity level, which in turns impacts their mortality. Absolute risk of 4-year mortality increases as patient activity levels decrease

,4 Hurst explained.

Diagnosis is a huge problem, Han said, because the majority of patients are already stage 2 or beyond based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) when they receive their diagnosis in the average practice. Hurst added that there are good data on who is at risk of developing COPD, but practitioners just need to be better at finding these patients.

One challenge is that patients have to feel comfortable discussing their symptoms in a guilt-free space, because there is the idea of self-blame with COPD, Hurst explained. They may have smoked or had other behaviors that led to their disease, and they blame themselves for their disease and may be hesitant to come forward with symptoms or downplay them.

For instance, one study found that 36% of patients who said they were too breathless to leave the house also described their symptoms as mild to moderate.5

“That’s astonishing,” Hurst said. “Too breathless to leave the house and yet that person feels the symptoms are mild to moderate. I was astonished when I saw that.”

More than half of patients report anxiety, social inhibition, or embarrassment because of their symptoms.6,7 Anxiety and breathlessness have close links, he said, and providers needs to not only think about the physical comorbidities associated with COPD—such as cardiovascular disease, chronic heart failure, or type 2 diabetes—but also mental health.

“Anxiety can be pervasive and difficult to manage,” Hurst said.

Looking at the guidelines for treatment, there are multiple guidelines to follow but they mostly say the same thing at the end of the day, Han said. GOLD suggests providers consider initially treating with long-acting muscarinic antagonist/long-acting beta agonist (LAMA/LABA) in patients with severe symptoms driven by dyspnea and/or exercise intolerance. The American Thoracic Society guidelines are a little stronger and have a strong recommendation to treat with a dual LAMA/LABA inhaler or over a monobronchodilator in the same patients.

For Han, patients who don’t have a lot of symptoms are probably okay on a monodilator, but more often she is starting patients on a dual bronchodilator because of how far along they are when she first sees them.

More data are coming out on mono vs dual bronchodilator therapy. On monotherapy, as much as 46% of patients may still experience dyspnea.8 Although the therapy is helping, it’s clear many patients would benefit from more therapy.

Research has shown that utilizing tiotropium/olodaterol vs monotherapy:

  • Reduces the intensity of breathlessness during walking9
  • Improves physical functioning after 6 weeks10

The dual bronchodilator also helps patients early in their disease and later in their disease. There is an improvement in lung function, health status, and breathlessness in maintenance-naive patients11 and in people who were on LAMA monotherapy at baseline.12

People tend to fixate on single end points, Hurst said, but “what we’re seeing is broad improvement” on dual bronchodilators.

Research also shows that the dual therapy had a 24% risk reduction of clinically important deterioration, defined as decrease in trough forced expiratory volume ≥ 0.1 L, increase in St. George’s Respiratory Questionnaire score ≥ 4 units, or occurrence of moderate/severe exacerbation.13 The reduction occurred in multiple subgroups:

  • Patients with low exacerbation history (27%)
  • Patients with GOLD stage 2 (28%)
  • Patients who are maintenance naive (25%)

An important consideration is preventing patients from moving up to triple therapy that includes an inhaled corticosteroid (ICS). The long-term use of an ICS has been associated with a number of adverse effects, such as pneumonia, oropharyngeal candidiasis, hoarseness, skin bruising, tuberculosis, cataracts, diabetes, and fractures, Han said. These side effects can really impact quality of life, and the decision to move patients onto ICS should not be taken lightly, because COPD is a chronic disease, she said.

“If we pick patients up earlier, they may be on medication for a very long time,” she said, and these risks accumulate. The risks really need to be weighed against the benefits.

Although not all patients will benefit from an ICS, there are some that really will, such as those with a history of exacerbations and with elevated blood eosinophil levels.14 Hurst added that the higher the blood eosinophil count, the more likely there is to be a benefit to patients who are on a regimen that includes an ICS. When a patient has a lower eosinophil count, providers should really question whether an ICS is necessary, he said.

“It’s the patients with really high eosinophil counts, as well as the really frequent exacerbations, that we want to think about when we’re trying to really decide risk vs benefit [of ICS] for these patients,” Han said.

Pharmacological treatments alone are not always enough. Dual bronchodilator therapy also boosts the benefits of exercise. One study15 found that tiotropium/olodaterol plus exercise training plus behavior modification (BM) increased exercise endurance time by 46% compared with tiotropium/olodaterol plus BM (29%) or tiotropium alone (4%).

The data suggest that the benefit a patient gets from exercise is enhanced if they are also on a dual bronchodilator, Hurst said. “So yes, pulmonary rehab is effective, but you can make it even more so by getting the bronchodilator right in the first place.”

References

1. Kessler R, Partridge MR, Miravitlles M, et al. Symptom variability in patients with severe COPD: a pan-European cross-sectional study. Eur Respir J. 2011;37(2):264-72. doi:10.1183/09031936.00051110

2. Miravitlles M, Worth H, Soler Cataluña JJ, et al. Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study. Respir Res. 2014;15(1):122. doi:10.1186/s12931-014-0122-1

3. Hurst JR, Vestbo J, Anzueto A, et al N Engl J Med. 2010;363(12):1128-1138. doi:10.1056/NEJMoa0909883

4. 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. doi:10.1378/chest.10-2521

5. Rennard S, Decramer M, Calverley PMA, et al. Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey. Eur Respir J. 2002;20(4):799-805. doi:10.1183/09031936.02.03242002

6. O’Hagan P, Chavannes NH. The impact of morning symptoms on daily activities in chronic obstructive pulmonary disease. Curr Med Res Opin. 2014;30(2):301-314. doi:10.1185/03007995.2013.857648

7. Stephenson JJ, Cai Q, Mocarski M, Tan H, Doshi JA, Sullivan SD. Impact and factors associated with nighttime and early morning symptoms among patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2015;10:577-586. doi:10.2147/COPD.S76157

8. Hahn B, Stanford RH, Goolsby Hunter A, Essoi B, White J, Ray R. Patient-reported burden of illness in a prevalent COPD population treated with long-acting muscarinic antagonist monotherapy: a claims-linked patient survey study. Pulm Ther. 2019;5(1):69-80. doi:10.1007/s41030-019-0091-0

9. Maltais F, Aumann J-L, Kirsten A-M, et al. Dual bronchodilation with tiotropium/olodaterol further reduces activity-related breathlessness versus tiotropium alone in COPD. Eur Respir J. 2019;53(3):1802049. doi:10.1183/13993003.02049-2018

10. Valipour A, Tamm M, Kociánová J, et al. Improvement in self-reported physical functioning with tiotropium/olodaterol in central and eastern European COPD patients. Int J Chron Obstruct Pulmon Dis. 2019;14:2343-2354. doi:10.2147/COPD.S204388

11. Buhl R, de la Hoz A, Xue W, Singh D, Ferguson GT. Efficacy of tiotropium/olodaterol compared with tiotropium as a first-line maintenance treatment in patients with COPD who are naïve to LAMA, LABA and ICS: pooled analysis of four clinical trials. Adv Ther. 2020;37(10):4175-4189. doi:10.1007/s12325-020-01411-0

12. Buhl R, Singh D, de la Hoz A, Xue W, Ferguson GT. Benefits of tiotropium/olodaterol compared with tiotropium in patients with COPD receiving only LAMA at baseline: pooled analysis of the TONADO and OTEMTO studies. Adv Ther. 2020;37(8):3485-3499. doi:10.1007/s12325-020-01373-3

13. Rabe KF, Chalmers JD, Miravitlles M, et al. Tiotropium/olodaterol delays clinically important deterioration compared with tiotropium monotherapy in patients with early COPD: a post hoc analysis of the TONADO trials. Adv Ther. 2021;38(1):579-593. doi:10.1007/s12325-020-01528-2

14. Langham S, Lewis J, Pooley N, et al. Single-inhaler triple therapy in patients with chronic obstructive pulmonary disease: a systematic review. Respir Res. 2019;20(1):242. doi:10.1186/s12931-019-1213-9

15. Troosters T, Maltais F, Leidy N, et al. Effect of bronchodilation, exercise training, and behavior modification on symptoms and physical activity in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(8):1021-1032. doi:10.1164/rccm.201706-1288OC