Long-term intervention in childhood asthma

In this thesis we first describe what is known from the literature on the effect of asthma drugs on airway responsiveness to histamine and methacholine (Chapter II). Chapter Ill describes the results of an acute effect study of an inhaled corticosteroid on AHR (sensitivity) to methacholine. In Chapter IV a study in children in which the effect of an inhaled corticosteroid was compared with the effect of a beta,-agonist on airway caliber, airway responsiveness to methacholine and symptoms during a period of 6 months is described. Chapter V describes the results of the first part of the multicenter study, in which the effect of long-term treatment with an inhaled beta,-agonist plus an inhaled corticosteroid was compared with the effect of an inhaled beta,-agonist-only on clinical endpoints, airway caliber, bronchodilator response and airway responsiveness to histamine. This part had to be discontinued after a median treatment period of 22 months because of the high withdrawal rate in the beta,agonist- only group. The second part of the study was concerned with the continuation of the patients on beta,-agonist plus inhaled corticosteroid up to 28 to 36 months after randomization, in which the further course of endpoints was studied and the remission rate was evaluated. The results are described in Chapter VI. The third part deals with the effect of cessation of inhaled corticosteroid in those children on inhaled corticosteroid who had a follow-up of at least 28 months on July 1, 1991 (Chapter VII)

Inhaled corticosteroids and growth of airway function in asthmatic children

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. (beta2-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