Longitudinal outcome of childhood asthma into adult life: outcome at 50 years

© 2010 Dr. Andrew shong Ngee TaiAsthma is one of the commonest conditions affecting the Australian and worldwide population and a significant level of knowledge about its natural progression from childhood into adulthood has been established from the Melbourne Epidemiological Study of Childhood Asthma (MESCA). This study randomly selected children who were born in Melbourne, Australia in1957 and has followed them up every 7 years to the current study whereby the participants are now 50 years of age. This study has provided a significant contribution to knowledge of the outcomes of childhood asthma into adult life. The hypothesis of the study was that children with severe asthma will have persistent symptoms into adult life and reduced lung function when compared to those who were healthy controls or had wheezy bronchitis, and that there was an association between children with severe asthma and adult chronic obstructive pulmonary disease in adult life. The first aim of the study was to describe the clinical outcome of childhood asthma at the age of 50 years and determine the factors that promote persistence or remission of asthma symptoms. The second aim was to monitor and track the change in lung function secondary to childhood asthma and examine the factors that may affect its rate of decline in adult life. Such factors include the severity of childhood asthma, sex, smoking history, asthma remission and bronchial hyperresponsiveness. There is also increasing evidence that childhood asthma may predispose subjects to the development of chronic airflow limitation in adult life. Lung function declines through adult years, and children with asthma, who may have deficits in lung function from early life, are likely to reach a threshold of symptomatic chronic airflow limitation at an earlier age than those without asthma. Therefore the final aim of the study was to assess for a possible relationship between childhood asthma and the subsequent development of adult chronic obstructive pulmonary disease (COPD). In this longitudinal study, 346 subjects participated from a cohort of 479 remaining survivors, representing a participation rate of 76%. Subjects underwent an interviewer-administered questionnaire, validated health-related quality of life questionnaires, objective lung function testing with bronchodilator response and skin prick testing as a means to measure atopy. The results of this study demonstrate that children who have more severe patterns of asthma in childhood will continue to have symptoms at the age of 50 years and reduced lung function when compared to children with intermittent asthma (wheezy bronchitis) or those without asthma (i.e. control group). Risk factors that determine the persistence of childhood asthma into adult life include severe asthma as a child, female sex and childhood hay fever. Children with severe asthma have established lower lung function from childhood years when compared to the controls and those with wheezy bronchitis and the deficits track throughout adult life. Importantly, there was no increase in the rate of decline in lung function in children with severe asthma compared to those with wheezy bronchitis or the control group despite the persistence of symptoms. The rate of decline in lung function was not affected by gender, history of smoking at the age of 21 or 50 years, asthma “clinical remission” status at age 50 years or bronchial hyperresponsiveness at the age of 28 years. Children with severe asthma are also at increased risk to developing chronic airflow limitation or chronic obstructive pulmonary disease by the age of 50 years, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Interestingly, a proportion of these children did not have a smoking history suggesting a phenotype of COPD which is related to childhood asthma. The children who developed COPD at age 50 had reduced lung function measurements from childhood years but again, there was no increase in the rate of decline in lung function throughout their adult years, when compared to those who were in the control group or had active asthma. The findings presented in this thesis confirm that lung function in adult life is determined in childhood and is reduced in children with asthma. This would suggest that airway remodeling, a process that occurs within the structural components of the airways in response to inflammation, begins in early life. Therefore, research into determining the factors that contribute to airway remodeling in infants and preschool children needs to be highlighted. Childhood risk factors that determine the persistence of asthma at the age of 50 years include childhood severe asthma, female sex and allergic rhinitis. Attention to the interplay of female gender and allergic rhinitis on the persistence of asthma is of interest as it will provide greater understanding towards asthma pathogenesis and highlight potential disease-modifying therapeutic options. There is also emerging evidence of a link between the outcomes of severe childhood asthma and adult chronic obstructive pulmonary disease, represented by fixed airflow obstruction. The absence of a smoking history supports the heterogenous nature and varying phenotype of this adult disease entity. To further define this relationship, longitudinal measurements of airway wall inflammation from childhood to adulthood, ideally by non-invasive techniques would be helpful. Clearly, if children with severe asthma are at risk of developing adult chronic obstructive pulmonary disease, longitudinal surveillance of these children needs to continue, especially if therapy with inhaled corticosteroids has been instituted