Asthma

Course of Disease

Heterogeneity

Asthma is a common, chronic inflammatory lung condition associated with variable airflow obstruction and symptoms of breathlessness, cough and wheeze. Age of onset, severity and clinical course varies between patient groups, and these clinical phenotypes are likely to reflect differences in the genetic, developmental and environmental factors which predispose to disease and trigger symptoms. Currently, these factors are not well understood, but they are likely to be vital in determining which patients go on to experience worsening disease outcomes and which patients respond to certain treatment regimes.¹

Early childhood

Longitudinal studies have consistently confirmed that most cases of chronic, persistent asthma start in early childhood, with the initial presentation occurring during the first 5 years of life.¹

Adolescent to adulthood

Over 60% of children who are frequently wheezy or who have a physician diagnosis of asthma go on to experience asthma-like symptoms as an adolescent. Chronic asthma symptoms that persistent into adolescence and early adulthood are associated with both sensitization to allergens and elevated levels of circulating IgE.¹

Asthma remission or progression

Severity and frequency of symptoms in early childhood predict outcomes in adulthood. Those that experience mild and infrequent symptoms in early life go on to experience no or mild asthma-related symptoms. Those with the most severe symptoms have persistent severe asthma in later life. In one population-based study, 52% of children (aged 10) with asthma and 72% of children with severe asthma had frequent or persistent wheeze age 42.¹

Deficits in lung volumes during childhood are also consistently associated with persistent asthma in adulthood. The presence of abnormal lung function in childhood is a predictor of asthma and children who wheeze or who have a diagnosis of asthma, who then go on to have persistent asthma in adulthood have reductions in FEV₁ and FEV₁/ FVC ratio compared with controls throughout life. Interestingly, the slope of decline over time does not alter between wheezers and controls in this group, suggesting that developmental factors are important in asthma sustainment in this group, but that these factors do not contribute to accelerated decline in lung function in later life.¹

In contrast to this, when asthma symptoms occur in later life (aged over 25 years), they are associated both with moderate deficits in FEV₁ and FEV₁/FVC in early adulthood and a faster decline in lung function in subsequent years. This, combined with studies of inflammation, suggest that in this group, developmental factors combined with epigenetic influences such as inflammatory polymorphisms or environmental stimuli, lead to progressive disease. Airway hyper-responsiveness appears to be an important component of this, and has been consistently associated with progression to adult asthma in a number of studies.¹

Re-emergence

Less is known about factors that cause the re-emergence of asthma following a period of remission in early adulthood. There is evidence that remission may be a clinical phenomena rather than a true abatement of disease, as it is not associated with a loss of inflammation or bronchial hyper-responsiveness. Indeed, eosinophil counts, exhaled nitric oxide and concentrations of IL-5 remain higher in asthma patients with no symptoms who are off treatment than sex and age-matched controls.¹