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1 Division of Respiratory Medicine, Dept of Pediatrics, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, 2 National Institute of Public Health and the Environment, Bilthoven, 3 Dept of Biostatistics and 4 Physiology Dept, Leiden University Medical Center, Leiden, 5 Asthma Center Heideheuvel, Hilversum, 6 Division of Respiratory Medicine, Dept of Pediatrics, Groningen University Medical Center, Groningen, the Netherlands. 7 Formerly of these institutions
CORRESPONDENCE: P.J.F.M. Merkus, Sophia Children's Hospital, Erasmus University Medical Center Rotterdam, 3000 CB Rotterdam, The Netherlands. Fax: 31 104636772. E-mail: p.j.f.m.merkus@erasmusmc.nl
Keywords: Airway function, asthma, bronchodilation, inhaled corticosteroids, lung growth, remodelling
Received: March 20, 2003
Accepted January 5, 2004
This study was supported by the Netherlands Health Research Promotion Program (SGO).
Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS).
Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7–16 yrs), who inhaled 0.2 mg salbutamol t.i.d. and 0.2 mg budesonide t.i.d. (ß2-agonist (BA)+ICS), or placebo (PL) t.i.d. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children.
Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL.
Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment.
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