Growing up with asthma

The two thirds with milder symptoms should grow out of asthma

Childhood asthma has been regarded as relatively benign and a condition that children often “grow out of.” Recently, however, investigators have reported higher prevalence of asthma in children1 2 and more frequent persistence of childhood asthma into adult life.3 Hence further studies on factors predicting remission or persistence of childhood asthma, and the development of adult asthma, are welcomed.

Two papers in this week's journal describe outcomes of asthma in cohorts of Australian children. Both longitudinal studies began in the 1960s and both followed up children recruited at age 7 until their 30s. One might therefore expect the findings of the two studies to be similar. Nevertheless, Jenkins et al conclude that “children with asthma reported by their parents were more likely than not to be free of symptoms as adults” (p 90)4 while Oswald et al conclude that “many children do not grow out of asthma” (p 95).5 How could similar studies in similar populations come to seemingly opposite conclusions?

Jenkins et al followed up a birth cohort of 8700 7 year old Tasmanian children whose parents had originally completed a questionnaire inquiring about a history of wheezing and asthma, recent wheeze, frequency of episodes, age at onset, presence of hayfever, and smoking. All children were assessed by spirometry. A follow up at 29-32 years, 1000 of those with parent reported asthma or wheezing were selected, together with 1000 others; 87% were located, and 75% provided information on their current respiratory status.

Four major conclusions can be drawn from this study. Firstly, a high proportion of asthmatic children become symptom free. The symptoms of fewer than one in three asthmatic children persisted into the fourth decade. Secondly, asthma in adults can be partially predicted from childhood asthma, especially from those features reflecting severity of the childhood disease. Those with childhood asthma were 2.5 times more likely to have adult asthma than those with no such history. In those with persistent disease, risk factors included female sex, onset after age 2, more than 10 attacks throughout childhood, lower peak flow rates in childhood, and parental asthma.

Thirdly, atopy is a major determinant of the outcome, with personal and parental histories of atopy being more commonly associated with frequent, current asthma in adulthood. Fourthly, new asthma in adulthood is not uncommon. One in nine children not reported as having asthma at age 7 developed asthma by age 30. Female sex, maternal hay fever, and lower lung function at age 7 were important risk factors for this. The most impressive abnormality of lung function in children who developed asthma in adulthood was a lower mid-expiratory flow, suggesting that small airway disease is predictive of adult asthma.

In contrast, the emphasis of Oswald et al's paper is that most childhood asthma persists. This report comes from Melbourne children who were recruited in the 1960s and reviewed at age 35. Methodological differences explain the different findings. The cohort was selected from the population of 7 year olds, but when reviewed at age 10 the cohort was “enriched” with children with more severe asthma (asthma with an age of onset below 3 years, with persistent symptoms, and either chest wall deformity or low lung function at age 10). These characteristics might be expected to predict more persistent asthma, and the finding that 70% of those with severe asthma at age 10 had persistent asthma at 35 is therefore not surprising. Others have reported similarly higher levels of symptoms persisting in people who had attended asthma clinics when children.6 But even among the Melbourne subjects with severe childhood asthma, 10% were fully symptom free as adults and 15% had only minimal symptoms. Jonsson and Boe similarly reported that up to a half of children admitted to hospital with asthma were symptom free as adults.7

If the Melbourne sample with wheezing, wheezy bronchitis, or asthma at age 7 is examined before the enriched subsample was added it is apparent that only 20% of subjects had persistent adult asthma likely to be clinically important. Of those with “wheezy bronchitis,” only a third had any symptoms at 35. This is consistent with “growing out of” mild asthma or wheezing, and the frequent persistence of more severe asthma. Interestingly, among Melbourne children with mild asthma, atopy was not a prognostic factor. This finding differs not only from that of the Tasmanian study, but also from other studies in Australia,8 New Zealand,9 Scandinavia,10 and Britain.11 Atopy was very common in the Melbourne cohort (99% in those with more severe disease), which makes the effect of atopy more difficult to determine. Prognosis of childhood asthma in the Netherlands, however, was likewise apparently not influenced by the presence of atopic disease.12 13

Other risk factors for persistent asthma in adults include airway hyperresponsiveness in childhood,12 but the present reports do not address this. Most studies show that persistent asthma is more likely in females. The likelihood of a low forced expiratory volume at one second in adulthood is related to the degree of abnormality of forced expiratory volume in childhood.14 15

Neither of these Australian papers addresses the impact of treatment on “natural” course. The favourable outcome for over two thirds of asthmatic children should influence long term studies of treatment. It is logical to study the efficacy of treatment in those at greater risk of persistent disease rather than in those who will probably grow out of their disease. Jenkins et al argue the benefits of treating children at higher risk, but the absence of substantiating evidence highlights the need for well controlled, long term studies of intervention in childhood asthma.

These two longitudinal studies therefore yield essentially consistent outcomes: about two thirds of children will out grow their disease (especially those with mild asthma), while the third with more severe asthma will have persistent symptoms in adult life. Risk factors for persistence have been identified: the challenge now is to determine whether managing these “at risk” children more intensively alters the outcome.