Merkus PJFM, van Pelt W, van Houwelingen JC, et al. Eur Respir J. 2004;23:861–868
Purpose of the Study.
To investigate the growth of airways and airspaces in children with moderate asthma who were treated at random with inhaled placebo or corticosteroids in a fixed dose irrespective of symptoms.
Patients with moderate to severe persistent asthma who participated in a clinical trial recruited between 1988 and 1992 from outpatient clinics for respiratory medicine of Juliana Children’s Hospital (The Hague, Netherlands) and Rotterdam University Hospital/Sophia Children’s Hospital (Rotterdam, Netherlands).
Every 4 months for up to 3 years, lung function was assessed in 54 asthmatic children (initial age: 7–16 years) who inhaled 0.2 mg of salbutamol three times daily and 0.25 mg of budesonide three times daily (β2-agonist [BA] + inhaled corticosteroid [ICS]) or placebo (PL) three times daily (BA + PL) in a randomized, double-blind design. Measurements were conducted before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in 1 second and of maximal expiratory flows at 60% and 40% of total lung capacity (TLC) relative to TLC as measures of 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 with healthy subjects, whereas in patients on BA + ICS a marked improvement was observed. 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 caliber of central and intermediate airways to subnormal within 2 months, but postbronchodilator small-airway patency remained reduced but improved compared with patients on BA + PL.
Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The reduced postbronchodilator patency of peripheral airways may reflect remodeling or insufficient anti-inflammatory treatment.
This study shows that treatment with ICS can improve several measures of lung function and promote normal lung growth in asthma but also demonstrates that residual functional abnormalities may present in asymptomatic children with asthma even with daily doses of ICSs. This suggests that anti-inflammatory treatment of children with asthma based on symptoms alone may not be enough to result in normalization of postbronchodilator airway function. There may be some ethical and practical considerations in treatment of asthmatic children in the absence of respiratory symptoms, and additional study is required to determine what is best for long-term optimal prognosis.