Distinguishing asthma and chronic obstructive pulmonary disease: why, why not and how?

The Dutch hypothesis that asthma, chronic bronchitis and emphysema should be considered as different expressions of one disease entity has been unpopular for several decades, but is now looking increasingly appealing as a potential explanation for the spectrum of airway behaviour in asthma and COPD. The interaction between atopy, infection, environmental insults and genes is critically important in both diseases. Although one or more of these features may predominate, the summative effect critically determines the severity of the disease in both asthma and COPD. Both diseases result from interactions between genes and the environment. In both, smoking contributes significantly to the risk of decline in lung function and suboptimal response to anti-inflammatory medication.4,5

The argument in favour of considering the two diseases as one is a pragmatic one. We have not been successful in developing diagnostic algorithms to usefully distinguish asthma from COPD. While variable airflow obstruction is proposed as a defining characteristic of asthma, it doesn’t always separate asthma from COPD, especially in older people with longstanding disease.6,7 Inflammatory features may not be helpful, as the inflammatory response is heterogeneous in both diseases — an eosinophil or neutrophil infiltration can occur in both. The limitations of biopsy sampling can make it difficult to identify the predominant inflammatory pattern, and different cells may predominate at different stages of each disease.

The arguments in favour of considering the two diseases on a continuum also extend to treatment. We tend to use the same drugs, with variations in emphasis. The goals of treatment are similar — to reduce symptoms, maintain lung function and normal activity, prevent exacerbations, reduce mortality and minimise the adverse effects of treatment. Asthma is optimally treated with anti-inflammatory medications, and bronchodilators are used as needed. COPD is usually treated with bronchodilators, which provide small symptomatic benefits, and inhaled corticosteroids, which reduce exacerbations and improve quality of life.1,6 Both diseases are treated by avoiding exposure to initiators and triggers. Acute exacerbations are frequently triggered by viral infections and are managed with maximal doses of corticosteroids and bronchodilators. Dealing with each of these simply by assessing the severity of airway obstruction and the response to treatment would be simple, would provide a clear guide to management, and would not necessarily result in poorer outcomes. This is thought to be particularly true for patients with longstanding asthma, which may be clinically indistinguishable from COPD and show much less impressive responses to asthma treatment.4,7

Despite their similarities, there are critical differences between asthma and COPD that influence management and prognosis. The natural histories of COPD and asthma differ significantly. Patients with COPD experience an inexorable decline in lung function, and, as their airway obstruction worsens, exacerbations become more frequent. In contrast, patients with asthma may have frequent exacerbations without decline in lung function. A defining feature of asthma is spontaneous variability of airway obstruction, and patients are often symptomatic when they have near-normal lung function. Most patients with COPD do not become symptomatic or aware of impairment until the forced expiratory volume in 1 second (FEV1) has fallen to about 50% of the predicted value. This frequently delays their diagnosis and has critical consequences for their quality and quantity of life,8,9 partly because motivation to stop smoking is increased by recognising its damaging effects. Patients with asthma do not normally experience lung function deterioration if they maintain regular anti-inflammatory medication, whereas patients with COPD continue to lose lung function despite medication. Once COPD is established, the only interventions that influence life expectancy are smoking cessation and oxygen therapy. By contrast, most patients with asthma have a normal life expectancy if they maintain regular preventive medication, and in older people, even those with severe asthma have a better outlook than those with COPD.10 Dyspnoea in patients with COPD is predominantly triggered by exertion, but in asthma there are usually many additional triggers, including allergens, cold air and non-specific irritants.

The end stages of COPD are characterised by the development of complications, particularly pulmonary hypertension and right heart failure. Many patients with COPD develop hypercapnia and respiratory failure. These are unusual outcomes for patients with asthma, even when there is severe airway obstruction, although comorbidities in both diseases may play an important role in determining outcome.

There are crucial differences in short-term and long-term responses to treatment. Objections to making a distinction between asthma and COPD are often made on the basis of the overlap in bronchodilator responses seen in both diseases. However, this occurs mostly in people with longstanding, poorly treated asthma or those in whom both diseases are present (“mixed disease”). Airflow limitation in COPD is not fully reversible. Although reversibility in response to bronchodilator may be significant and FEV1 may improve by more than 10%, the ratio between FEV1 and vital capacity (FEV1/VC) does not return to the normal range in COPD, as it usually does in newly diagnosed asthma. The histopathology of asthma and COPD is markedly different, resulting in different physiological characteristics. Emphysema is associated with dilated air spaces and a progressive fall in gas transfer, which rarely occur in asthma. The accelerated loss of lung function that characterises COPD, despite treatment, is not a common feature of asthma.

Choice of treatment also differs significantly, even though similar drugs are used in both diseases. There is strong evidence in asthma for an effect of low-dose inhaled steroids on exacerbations, quality of life, lung function, symptoms and mortality. In COPD, inhaled steroids do not affect lung function decline, and only high-dose inhaled steroids have been shown to affect exacerbation rate at the later stages of the disease. However, pulmonary rehabilitation has a significant impact on quality of life and exercise performance in patients with COPD.

Prognosis differs between the two diseases, particularly when FEV1 is less than 1 L. The risk of death from COPD is closely related to the degree of impairment of ventilatory function as expressed by FEV1. FEV1 also predicts the likely need for long-term oxygen therapy, the increasing frequency of exacerbations and hospital admissions, and the likely development of pulmonary hypertension.