Counteract exacerbations and improve quality of life

To achieve a reduction in the frequency of exacerbations – a primary therapeutic goal in COPD – a multimodal therapy concept is recommended. Regarding bronchodilator inhalation therapy, SABA and SAMA are nowadays recommended only as on-demand medication; long-term therapy is with LABA and LAMA. In certain cases, dual or triple therapy containing cortisone is also useful. Patient education, smoking cessation, and pulmonary rehabilitation are other important treatment components.

Patients who are diagnosed with COPD (chronic obstructive pulmonary disease) complain most frequently of shortness of breath. Dyspnea is a momentous symptom. There may be a reduction in activity and social withdrawal, accompanied by a decrease in performance and an increased risk of anxiety and depressive symptoms. “It is important to break this downward spiral at an early stage,” says Carolin Steinack, MD, Senior Physician, Department of Pneumology, University Hospital Zurich [1]. According to the WHO, COPD is now the fourth leading cause of death worldwide. “Early diagnosis and treatment is certainly an important goal,” she said [1].

Smoking cessation and pulmonary rehabilitation – elementary but important.

Although there are other risk factors such as genetic factors, early childhood events, acquired infections, and environmental factors, cigarette smoking remains the most common cause of COPD in Europe [2]. “Please actively ask about smoking,” Dr. Steinack emphasized [1]. This also applies to relapses in the course of therapy. Patients may need assistance in quitting smoking. However, COPD is also associated with extrapulmonary involvement. Pulmonary rehabilitation – another important lifestyle intervention for COPD – is also about exercising muscles and conditioning to reduce dyspnea and cardiovascular limitations. He said it is important for COPD patients to be encouraged to engage in activities early on while still hospitalized or to participate in rehabilitation programs in the outpatient setting. That this is worthwhile is shown by a meta-analysis published in 2016 based on multiple randomized-controlled trials that included pulmonary rehabilitation after exacerbation [3]. “This meta-analysis, which included around 20 studies with over 1500 patients, was able to show that patients who receive rehab compared to those who do not receive rehab have a significant benefit,” the speaker reported [1]. This is shown by the analyses regarding quality of life (St George’s Respiratory Questionnaire, SGRQ) and 6-minute walk test. In addition, the risk of hospitalization due to another exacerbation in the first year after an exacerbation was massively reduced. In summary, pulmonary rehabilitation contributes to a reduction in morbidity and mortality.

Exacerbations are associated with worsening of lung function

Each patient should always be checked to determine the stage of disease and whether therapy needs to be adjusted, if necessary. The impact of exacerbations is considerable. Over 77% of all patients experience a severe or moderate exacerbation within the first three years of COPD diagnosis. Severe exacerbations often require hospitalization and threaten persistent pulmonary function impairment. Study findings indicate that lung function remains well below the individual normal level for 8 weeks after an acute exacerbation [4]. Each exacerbation may reduce the time to the next severe exacerbation or death [5]. One treatable trait is blood eosinophils. “Blood eosinophils are often associated with more severe and frequent exacerbations,” explained Dr. Steinack [1]. It is a correlate of the extent of inflammation in the bronchi. In the context of an individualized therapy, it is useful to determine the blood eosinophils (these correlate with sputumeosinophils) and, if necessary, to consider an extension of therapy in case of high eosinophilia.

Inhalation therapy – differentiate between on-demand and basic medication

An evidence-based treatment algorithm is shown in Figure 1 [12]. Short-acting anticholinergics (SAMA) and beta-agonists (SABA) are suitable for intermittent on-demand treatment in the early stages of the disease and, when appropriate, as an emergency medication for exacerbations, but not for basic therapy [6]. Instead, long-acting bronchodilators are recommended for this purpose: Long-acting anticholinergics (long-acting muscarinic-receptor antagonist, LAMA) and long-acting beta agonists (long-acting beta agonist, LABA) are the basic medications in symptomatic patients with mild or moderate obstruction with and without frequent exacerbations [6,7]. LAMA/LABA combination products are approved in Switzerland as second-line therapy for patients who continue to experience symptoms with monotherapy. LAMA/LABA combinations have shown a moderate additive effect over bronchodilator monotherapy in terms of lung function, quality of life, and exacerbation prevention.

Who benefits from cortisone dual or triple therapy?

ICS/LABA combination is indicated in patients with COPD only under certain conditions: Moderate to severe COPD with at least one moderate exacerbation per year or when asthma-COPD overlap is present. In symptomatic patients who had at least one severe exacerbation in the past 12 months despite maintenance therapy with LAMA+LABA or LABA+ICS, treatment with a triple combination of ICS/LAMA/LABA seems to have an additional effect on the exacerbation rate compared with the dual combination [6]. This is evident, among other things, from the IMPACT study [8,9]. This was a randomized-controlled multicenter parallel-group study (n=10 355) with three study arms. Both annual exacerbation and mortality rates were significantly reduced by triple therapy with fluticasone furoate/umeclidinium/vilanterol compared with umeclidinium/vilanterol and compared with fluticasone furoate/vilanterol in symptomatic COPD patients with at least one severe exacerbation in the past year [1,8,10,11]. Cases requiring hospitalization were assessed as severe exacerbations. Furthermore, there is evidence that patients with an eosinophilia ≥150 cells/μl to at baseline particularly benefit from cortisone triple therapy.

Literature:

1. «Früher Behandlungsbeginn und relevante Eskalation im Management von COPD», Dr. med. Carolin ­Steinack, FomF Fortbildung, WebUp, 15.06.2023.
2. Stolz D, et al.: Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. Lancet 2022; 400(10356): 921–972.
3. Puhan MA, et al.: Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2016 Dec 8;12(12): CD005305.
4. Watz H, et al.: Spirometric changes during exacerbations of COPD: a post hoc analysis of the WISDOM trial. Respir Res 2018; 19(1): 251.
5. Suissa S, Dell’Aniello S, Ernst P: Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax 2012; 67(11): 957–963.
6. COPD, www.medix.ch/wissen/guidelines/copd,(last accessed 07/12/2023).
7. Agustí A, et al.: Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Am J Respir Crit Care Med 2023; 207(7): 819–837.
8. Pascoe SJ, et al.: A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol. Eur Respir J 2016; 48(2): 320–330.
9. Lipson DA, et al.: IMPACT Investigators. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med 2018; 378(18): 1671-1680.
10. Lipson DA, et al.: Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Pa­tients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2020; 201(12): 1508–1516.
11. GOLD Report 2020, http://goldcopd.org, (last accessed 12.07.2023)
12. Nationale Versorgungsleitlinie COPD, 2021,
    www.leitlinien.de/themen/copd/2-auflage/kapitel-5,(last accessed 07/12/2023).

HAUSARZT PRAXIS 2023; 18(8): 30–31