By Porntiva Poorisrisak, MD, PhD
Chairman: Henrik Verder
Opponent: Henrik Permin
Opponent: Per M. Gustafson
The Ph.D. thesis is based on studies conducted at 6 pediatric departments in following hospitals: Naestved, Gentofte, Kolding, Skejby, Hvidovre and Rigshospitalet.
Study I: Specific airway resistance (sRaw) measured by wholebody plethysmography in preschool children is increasingly used in research and clinical practise. However, there is no available method for calibration of the resistance measure, which raises concern of accuracy.
The primary aim was to determine the agreement of sRaw measurements in 6 centers. Seven healthy young children were brought to each of the 6 centers for sRaw measurements and measured by a center specific investigator as well as an investigator visiting each center.
We found sRaw measurements at two centers were significantly lower in all children compared to the other 4 centers and one center had significantly higher sRaw values than the other centers.
The secondary aim was to expand normative sRaw values for non-asthmatic children in 5 centers. 105 healthy preschool children were recruited locally for sRaw measurements. Normative data was generated and was without significant difference between centers and independent of height, weight, age and gender. Furthermore, there was no effect of the child’s history of atopy, parental atopy or smoking. We subsequently pooled these normative data (105 children) with previous data from 121 healthy young children; mean sRaw (SD) 1.27 kPa*s (0.25).
Conclusion: Control using biological standards revealed errors in factory setting and highlights the need for developing methods for verification of resistance measures to assure accuracy. Normative data were subsequently generated. Importantly other centers using such normative data should first consider proper calibration before applying reference values.
Study II-III: Acute respiratory syncytial virus (RSV) bronchiolitis may occur in otherwise healthy infants. It is not known whether viral bronchiolitis is causatively related to asthma or simply identifies infants at risk for subsequent wheezing from an atopic predisposition or pre-existing abnormal lung function.
First aim was to determine the differential effect within monozygotic twin (MZ) pairs discordant for severe RSV bronchiolitis in infancy on the subsequent development of asthma, pulmonary function and allergy. 37 MZ twin pairs discordant for RSV hospitalization in infancy were compared at the mean age of 7.6 years for lung function and bronchial responsiveness. We found no differences within MZ twin pairs with respect to pulmonary function, fractional exhaled nitric oxide, asthma prevalence, asthma medication use, or sensitization.
Secondary aim was to compare prospectively the baseline lung function and bronchial responsiveness in infants who later develop RSV bronchiolitis with infants who do not develop such severe infection. In a prospective birth cohort study of 411 infants of asthmatic mothers 22 infants developed RSV bronchiolitis. Infants with and without RSV bronchiolitis did not differ significantly in baseline lung function or bronchial responsiveness.
Conclusion: We found no effect of severe RSV bronchiolitis on the development of asthma and abnormal pulmonary function, nor did baseline lung function seem to predict later development of RSV bronchiolitis. This ague against a specific effect of the RSV bronchiolitis in the development of asthma and may suggest a genetic factor or an undisclosed environmental predisposing to severe RSV bronchiolitis, maybe co-infection rather than mechanical difference as the distinguishing feature for the development of RSV bronchiolitis.