Update on COPD

Prevalence

Moderate and Severe COPD affects one in 10 people

The prevalence of COPD is increasing in Ireland, and COPD is expected to be the third cause of death by 2020. BOLD, a worldwide study including close to 10,000 participants, aimed to measure the prevalence of COPD, its risk factors and their variation across countries by age, sex, and smoking status.^{1, 2} The results, published in the Lancet, showed higher COPD levels and more advanced staging than typically reported, with a prevalence of GOLD stage II or higher COPD of 10.1% overall (11.8%  for men, and 8.5% for women). Among those, 23.3% were never smokers, two thirds being women, and the vast majority previously undiagnosed. This suggests that, although age and smoking are strong contributors to COPD, they do not fully explain variations in disease prevalence. Other factors are important and their understanding is critical to develop optimal prevention.

Non-smoking related factors

Current evidence increasingly emphasises the non-smoking causes of COPD.  It is now estimated that 20 to 25% of COPD is non-smoking related – a figure which is likely to be even higher in developing countries.  Though more evidence is needed, it points towards a wide range of factors which are:

• Genetic –  Limited evidence of familial aggregation of pulmonary function among non-smokers and identification of a few genetic determinants.
• Environmental – a) Association between outdoor pollution and a decrease in pulmonary function growth during childhood and adolescence – b) Role of biomass well established in women, where multiple studies have linked biomass smoke exposure with chronic bronchitis and COPD.
• Occupational – Exposure-response gradients observed in epidemiological or prospective cohort studies.
• Comorbidities – Suggested association between chronic asthma and COPD as well as TB and COPD, though it is unclear whether these associated COPD are clinically similar as COPD from other causes.

Exacerbations

“A sustained worsening of the patient’s condition, from the stable state and beyond normal day-to-day variations… necessitates a change in regular medication”. ³

Exacerbations are key events in COPD due to their critical impact on disease progression.

They are a major cause of morbidity, mortality and hospital admission. Approximately 20-25% of patients admitted to hospital due to an exacerbation die within 1 year.

Exacerbations of COPD are thought to be caused by complex interactions between the host, bacteria, viruses and environmental pollution (50-70% due to respiratory infections and 10% to pollution), but a significant proportion (30%) are of unknown aetiology. ⁴ Although evidence shows a relation between frequency of exacerbations and COPD severity – the higher the GOLD stage, the more frequent the exacerbation –, their frequency also appears to reflect an independent susceptibility. ⁵ One of the biggest predictors of exacerbation frequency in any one year is the number of exacerbations within the previous year. Other predictors include decrease in FEV1, history of heartburn and white cell counts.

Reducing exacerbations

One important goal of COPD management is to reduce exacerbations, which is achieved by:

• Influenza and pneumonia vaccinations
• Regular exercise
• Pulmonary rehabilitation
• Inhaled therapy

There is evidence that exercise reduces the risk of COPD by modifying smoking-related lung function decline. A prospective study including close to 7000 participants showed that moderate and high levels of regular physical activity are associated with a reduced FEV1 and FVC decline compared to low physical activity (relative FEV1change of 2.6 and 4.8 ml/year) and  a reduced risk of developing COPD among smokers. ⁶

Pulmonary rehabilitation (PR) reverses the spiral of events starting with breathlessness, leading to inactivity, which causes muscle deconditioning and production of CO2 and lactate, which in turn contributes to increased breathlessness. PR has been demonstrated to improve walking distance, breathing and quality of life. In one study, pulmonary rehabilitation after acute exacerbations twice daily for 8 weeks resulted in very significant reduction in the proportion of patients readmitted (33% with usual follow-up care vs. 7% with PR). ⁷

Guidelines on inhaled therapies recommend to start with short bronchodilators (alone or in combination) before moving to long acting ones if symptoms persist. Recent placebo-controlled, double-blind, randomised clinical trials have reported positive results for a number of therapeutic options (see Table 1). These include:

• Combination long-acting beta2 agonist (salmeterol, formoterol) / inhaled corticosteroid (fluticasone)
• Tiotropium (anticholinergic)
• Indacaterol  (ultra-long-acting beta-adrenoceptor agonist)
• Azithromycin (macrolide)
• Roflumilast (PD4 inhibitor)

Table 1: Therapeutic options to reduce exacerbations – The clinical evidence

*Statistically significant

See also Suggested COPD Algorithm.

Key message:

• Evidence increasingly points towards the role of non-smoking factors in the development of COPD, including genetic, environmental, and occupational factors as well as comorbidities.
• Reducing exacerbations is a key challenge in the management of COPD. This can be achieved by the combination of smoking cessation, long-acting beta agonist / inhaled corticosteroid combination, exercise and pulmonary rehabilitation.
• New agents are also promising for the reduction of disease progression.

‘COPD – Where are we now?’ was presented among other respiratory topics at the Frontiers in Respiratory Medicine meeting, October 21^st, 2011.

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