© 2002 American Thoracic Society
Childhood Experiences Take Away Your Breath as a Young AdultReduced lung function is a feature of asthma, and asthma management guidelines aim at achieving (near) normal lung function in affected patients (1). Moreover, in many clinical studies baseline lung function, particularly the forced expiratory volume at 1 second (FEV1), is a primary endpoint for assessing potential benefits of asthma drugs. For example, the large Childhood Asthma Management Program (CAMP) study has been designed to evaluate whether continuous long-term treatment is superior to treatment for symptoms only with respect to lung growth measured as postbronchodilator FEV1 over a 4-year period (2). Neither treatment arm achieved improvement of lung function among these subjects and has given rise to considerable debate. In this issue of the AJRCCM (pp. 1480–1488), Rasmussen and coworkers (3) present the findings of a large prospective cohort study involving 1,037 subjects followed serially over two decades in New Zealand. The findings may help to partly explain the negative results of the CAMP study. Respiratory questionnaires were completed at ages 9, 11, 13, 15, 18, 21, and 26 years, and almost all subjects underwent lung function testing and methacholine challenge at these ages. Moreover, bronchodilator tests were performed in all subjects at ages 18 and 26. Finally, atopy was assessed by skin prick tests at ages 13 and 21. Three main messages can be deduced from these findings: First, lung function either expressed as FEV1 or FEV1/FVC ratio tracks over time. Accordingly, reductions in lung function at age 26 years can be traced back to decrements already established at age 9 years; in other words, the FEV1 at age 9 is a significant predictor of a low FEV1/FVC ratio at age 26. Therefore, one component of diminished lung function at any age is likely to relate to a subject's intrinsic airway and lung tissue properties that may underlie genetic control irrespective of any illness. The independent effect of FEV1 at age 9 in the multivariate model, presented in Table 7 of the article, supports this notion. Asthma before age 9 years may also have resulted in substantial decrements in lung function that subsequently track along predetermined paths. The authors do not present this information, but data from another large Australian cohort suggest that at age 7 years decrements in lung function according to asthma severity are already set and will not change thereafter (4). In the large prospective Tucson Children's Respiratory Study, differences between groups of subjects with and without asthma were already apparent at age 6 years, but not shortly after birth (5). This finding suggests that the disease process is likely to impact on airway and lung tissue growth and maturation in the first 5 to 6 years of life. This reasoning may in part explain why, in the CAMP study, treatment did not improve lung growth, as assessed by the postbronchodilator FEV1, because study subjects were already 9 to 11 years of age at enrollment, thus potentially too old to influence subsequent lung function growth. The second message relates to the importance of childhood asthma for the presence of impaired lung function in young adulthood. The authors do not present a truly longitudinal analysis of their data. Therefore, the reader does not know whether the duration of the illness or newly acquired asthma (both determine the prevalence of any illness) predicts reductions in pulmonary function. A hint is, however, given in Table 5 where the duration of the illness among men is shown to relate consistently to diminished lung function in early adulthood. Not only asthma, but also airway hyperresponsiveness without a diagnosis of asthma at age 9 years was a significant determinant of low lung function at age 26. Interestingly, in the multivariate model presented in Table 7, both asthma and airway hyperresponsiveness were independent predictors, suggesting that the adverse effect of asthma is not explained by airway hyperresponsiveness, but rather characteristics associated with both traits contribute to lung function decrements. In contrast, atopy, either measured as total immunoglobulin E or as skin test reactivity, was not related to lung function impairment. Atopic inflammatory responses may therefore play a bystander role attributable to the close association between asthma and atopy rather than causally contributing to the structural remodeling of airway and lung tissues. The findings of this large New Zealand cohort study in fact suggest that airway properties and alterations are the main predictors of lung function loss over time. Third, sex issues are not only important in social life, but matter also with respect to lung disease. The data from the New Zealand cohort corroborate previous findings (6–8), showing that lung function either expressed as pre or postbronchodilator FEV1/FVC ratio, or as a consistently low ratio between the ages of 18 and 26 years, is lower among male than among female subjects. Interestingly, the difference is also seen among subjects with asthma: 22.0% of men with current asthma at age 26 years have a low postbronchodilator ratio at that age, whereas only 10.5% of females with asthma show such impairment. The causes for the sex differences in this cohort can only be hypothesized. One potential explanation is the longer duration of asthma among men than among women (Table 5), suggesting that asthma was present at an earlier age among boys and thereby impacting on airways and lung tissue in the sensitive period of growth and maturation. In addition, differences in airway tone may exist because men showed greater bronchodilator reversibility than women. Studies such as those presented by Rasmussen and colleagues are invaluable for the understanding the natural history of asthma, lung function growth and decline, and eventually the development of COPD from childhood to adulthood. Much, but not all, is determined at a young age. Therefore, understanding the origins of asthma and lung function growth may help prevent the irreversible loss of pulmonary function and associated disease. Ongoing large studies investigating the potential of different medications to prevent lung function decline over preschool years may not only affect a pediatrician's life, but may also impact on an adult person's well being in the long run. ERIKA VON MUTIUS, M.D., M.SC. University Children's Hospital Munich, Germany REFERENCES
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
