By Henrik Wegener Hallas
Chariman: Peter Lange
Opponent: John Henderson
Opponent: Jørgen Vestbo
Asthma affects millions of children worldwide. The disease is characterized by troublesome lung symptoms, which hamper the child’s activities and result in reduced quality of life. The symptoms can be highly unpredictable and very diverse in severity and frequency, when worst some children will require intensified treatment and hospitalization, which leads to large health care expenditures.
Researching asthma is a difficult task, partly due to the lack of a clear definition and of a reliable diagnostic tool. Lung function measurements have proven useful when scrutinizing asthma, and longitudinal child cohorts with lung function measured since birth have taught us valuable lessons, e.g. that lung function is reduced before the onset of asthma symptoms.
Luckily, most children seem to grow out of their symptoms during childhood, but little is known regarding the development of lung function after cessation of symptoms and in general how asthma symptoms and lung function interrelate. The prevailing paradigm proposes that ongoing asthma disease has a detrimental effect on lung function in childhood, but indications exist that this is not straightforwardly.
The aims of this PhD thesis were to study lung function development from birth to adolescence in relation to asthma and exacerbations. The main goal in relation to this was to gain insight into the hen-or-egg question: Do asthma and exacerbations lead to impaired lung function or vice versa?
The studies in this thesis are based on Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000), a single-center prospective birth cohort of 411 children born to mothers with asthma. The children had lung function assessed as airway obstruction and reactivity by 8 different methods at 11 time- points from 4-weeks of age till adolescence.
In Study I we examined the longitudinal development of lung function from birth till adolescence in children who developed asthma compared to children without asthma. We found that children with asthma had increased airway obstruction and airway reactivity throughout childhood. This was present before onset, not improving after remission of symptoms, and not correlated with duration of disease.
In Study II we investigated lung function trajectories in children with asthma with vs. without exacerbations. We found that airway obstruction was increased in children with asthma with exacerbations throughout childhood compared to children with stable asthma without exacerbations. The exacerbations had an acute deteriorating effect on lung function but did not aggravate long-term lung function development.
In conclusion: We found that lung function is reduced throughout childhood in children who at some point develop asthma compared to children without asthma. Among the children with asthma, the ones with severe exacerbations have an even further reduced lung function throughout childhood compared to the children with stable asthma. Lung function in childhood seems to develop as stable traits established at birth and unaffected by onset, duration, and remission of possible asthma symptoms and exacerbations. These findings imply that asthma may in part be a consequence of these inborn traits but not their cause and that the frequency and severity of symptoms are related to the degree of lung function deficit. Thus parts of the explanation of childhood asthma and proneness to exacerbations should be sought in the earliest life, maybe even in utero, and preventive measures should be taken accordingly.