Treatment of severe small airways disease in children with cystic fibrosis: Alternatives to corticosteroids

A group of patients with cystic fibrosis (CF) have severe small airways disease characterized by wheeze, chest tightness and limited sputum production, often with deteriorating lung function. Suggested mechanisms include mucosal edema secondary to infection and inflammation, smooth muscle contraction caused by inflammatory mediators, and collapse of bronchiectatic airways. While treatment with long-term oral corticosteroids may result in symptomatic improvement, adverse effects often make them intolerable. Inhaled corticosteroids are used in many centers despite the lack of conclusive evidence of their efficacy. Therapeutic alternatives to corticosteroids are aimed at reversing bronchoconstriction and reducing inflammation. Many patients with CF are treated with short- and long-term inhaled bronchodilators, but data to support their use are inconclusive. Other attempted routes of administration for short-acting bronchodilators include the subcutaneous and intravenous routes, but clinical data are again lacking. Sodium cromoglycate (cromolyn sodium) has been studied, with little evidence of benefit. Theophyllines have also been studied, both intravenously and orally, with some effect, but are not often used in clinical practice. Nonsteroidal anti-inflammatory therapies include ibuprofen, macrolide antibiotics, intravenous immunoglobulin, cyclosporine, and leukotriene antagonists. Ibuprofen has been shown to be useful in patients with mild CF disease, but concerns about potential adverse effects have limited its use. The results of various macrolide studies are awaited, but to date there are no long-term studies published. While there is great interest in the potential of intravenous immunoglobulin, cyclosporine and leukotriene antagonists, the evidence for their effectiveness comes from anecdotal reports, thus there is currently insufficient data to support their use. Since this is a small group of patients, it is unlikely that sufficient numbers will ever be recruited for these studies; thus it is probable that drugs will be tried on an individual patient basis. The order in which they are attempted is unclear, but it would be sensible to try the least invasive medication with the least adverse effects first, moving on to more potent, but more toxic drugs if that treatment fails.