The prevalence of COPD is ~13.4% in Africa, with estimates of ~20% for South Africa. Tobacco smoking is the leading risk factor for COPD. Other risk factors include exposure to air pollution and long-term biomass fuel, as well as tuberculosis, and changes in season.^2,3

Patients living with COPD face increased mortality, higher rates of hospitalisation and exacerbation, and worse quality of life in cold weather seasons. This may be due to the fact that cold temperatures trigger exacerbations.⁴

New definition of COPD

GOLD 2023 defines COPD as: ‘A heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnoea, cough, expectoration, exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction’.¹

According to the authors, the new definition acknowledges the key pathogenic role of tobacco smoking but also accounts for other factors that contribute to COPD. Non-smoking COPD may be responsible for up to 60%-70% of cases.¹

Apart from the above-mentioned, the report highlights other risk factors such as:¹

• Lung development and ageing
• Socioeconomic status
• Asthma and airway hyper-reactivity.

New definition of exacerbations

The new definition of a COPD exacerbation is: ‘An event characterised by increased dyspnoea and/or cough and sputum that worsens in <14 days which may be accompanied by tachypnoea and/or tachycardia and is often associated with increased local and systemic inflammation caused by infection, pollution, or other insult to the airways’.

New opportunities for earlier COPD diagnoses

In terms of opportunities to diagnose COPD earlier, the report describes some patients who present with structural lung lesions and physiological abnormalities without airflow obstruction, who are categorised as having  pre-COPD.¹

The authors explain there are two main phenotypes of COPD (airway inflammation and emphysema), which could be different in clinical symptomatology and lung function alterations. Even with a normal forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio without airway obstruction, COPD can be present when this is confirmed by other findings (eg chest radiology). In some instances this could be the case in advanced disease.¹

Assessment of COPD

The major change that was made with regards to the assessment is the removal of Category C (exacerbations without symptoms), because it was not clinically relevant. Groups C and D have been merged into Group E (exacerbation prone) and highlights the clinical relevance of exacerbations.¹

Patients categorised as group A have modified Medical Research Council (mMRC) dyspnoea scale scores of 0–1, a COPD Assessment Test (CAT) score <10, and a history of zero or one moderate exacerbation not leading to hospitalisation.¹

Patients in group B have mMRC scores ≥2, a CAT score ≥10, and a history of zero or one moderate exacerbation not leading to hospitalisation. Patients in group E have a history of ≥2 moderate exacerbations or ≥1 exacerbation leading to hospitalisation, irrespective of their mMRC or CAT scores.¹ 

GOLD grades and severity of airflow obstruction

Chronic dyspnoea is a key symptom of COPD. Other symptoms indicative of a possible COPD diagnosis include sputum production (present in ~30% of patients), recurrent wheezing and chest tightness, intermittent chronic cough, recurrent lower respiratory tract infections, fatigue, and a history of risk factors (eg tobacco smoking).

Symptoms of severe COPD include weight and muscle mass loss, anorexia, and ankle swelling. When the diagnosis of COPD is confirmed by spirometry, the severity of the disease should be used to guide treatment decisions.¹

Table 1: GOLD grades and severity of airflow obstruction based on post-bronchodilator FEV₁

 Changes in the recommendations for initial pharmacological therapy

The overarching goals of stable COPD treatment are to relieve symptoms, improve exercise tolerance, improve health status, prevent disease progression, prevent and treat exacerbations, and reduce mortality.¹

According to the report when initiating treatment with long-acting bronchodilators, the preferred choice is a combination of a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA).  A high symptom burden of dyspnoea persists in most patients when using either a LAMA or LABA alone.¹

Additionally, the report states that the use of a LABA–inhaled corticosteroid (ICS) combination should not be encouraged in COPD. LABA–ICS has therefore been removed from recommended initial treatments, and LABA–LAMA should be initiated for patients in groups B and E. Triple therapy with a LABA+LAMA+ICS can be considered in Group E if eosinophil count is ≥300 cells/μl.¹

Superiority of tiotropium bromide

Tiotropium was the first LAMA available for COPD in clinical practice and, because of its long duration of action, is administered once daily. According to Anzueto and Miravitlles ‘no other LAMA has been proven superior to tiotropium, making it an optimal LAMA as monotherapy and as the backbone LAMA in LABA-LAMA combination therapy. 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’.⁵

In South Africa, tiotropium inhalation capsules are indicated for long-term maintenance therapy for patients living with COPD, including those with chronic bronchitis and emphysema.⁶

The Understanding Potential Long-Term Impacts on Function with Tiotropium study (UPLIFT), established that tiotropium use in patients with COPD resulted in three significant findings:⁷

• Participants of the experimental group receiving tiotropium had a reduced risk of COPD exacerbations
• When compared to the placebo group, the experimental group had an overall improved lung function and quality of life through the course of the four-year trial
• Tiotropium reduced respiratory and cardiac morbidity in COPD patients.

Subsequent studies showed that treatment of patients categorised as GOLD stage 1 and stage 2 using tiotropium resulted in a lower rate of disease progression as measured by post-bronchodilator FEV₁, suggesting that tiotropium use in early stages of COPD is beneficial.⁸

Other studies found that tiotropium use:^9,10,11,12

• Increases walking endurance exercise
• Improves exercise tolerance when used in combination with pulmonary rehabilitation
• Decreases COPD related hospitalisations
• Reduces air trapping and exertional dyspnoea (both of which are complications of COPD).

What about safety?

Findings of both short- and long-term randomised, controlled clinical trials in patients with COPD showed that tiotropium is safe and associated with significantly improved lung function, health-related quality of life, exercise endurance, and reduced dyspnoea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators.⁵ 

REFERENCES 

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2023 Report). https://goldcopd.org/2023-gold-report-2/
2. Koegelenberg CFN, van Zyl-Smith RN, Dheda K, et al. Position statement on endoscopic lung volume reduction in South Africa: 2022 update. Afr J Thoracic Crit Care Med, 2022.
3. Saieva P, Jenkins LS. When people do not 'Zol': Reduced emergency centre attendance of patients with chronic obstructive pulmonary disease during coronavirus disease 2019 lockdown with the accompanying tobacco sales ban in South Africa. Afr J Prim Health Care Fam Med, 2021.
4. McCormack MC, Paulin LM, Gummerson CE, et al. Colder temperature is associated with increased COPD morbidity. Eur Respir J, 2017.
5. Anzueto A, Miravitlles M. Tiotropium in chronic obstructive pulmonary disease – a review of clinical development. Respir Res, 2020.
6. Tiores. https://www.mobimims.co.za/Product/Index?id=1eab7821-46bf-4357-a762-d44727022cee&classificationid=49eddfe9-2f23-47be-9646-c2dd5d301e21
7. Tashkin DP, Celli B, Senn S, et al. UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med,
8. Zhou Y, Zhong NS, Li X, et al. Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease. N Engl J Med,
9. Decramer M, Celli B, Kesten S, et al. UPLIFT investigators. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet,
10. Bédard ME, Brouillard C, Pepin V, et al. Tiotropium improves walking endurance in COPD. Eur Respir J,
11. Casaburi R, Kukafka D, Cooper CB, et al. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD. Chest,
12. O'Donnell DE, Flüge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J,
13. ZuWallack AR, ZuWallack RL. Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease. Expert Opin Pharmacother, 2004.