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Anti-Inflammatory Medications for Cystic Fibrosis Lung Disease

Selecting the Most Appropriate Agent

  • Review Article
  • Published:
Treatments in Respiratory Medicine

Abstract

The lung disease of cystic fibrosis (CF) is characterized by a self-sustaining cycle of airway obstruction, infection, and inflammation. Therapies aimed at decreasing the inflammatory response represent a relatively new strategy for treatment. Attention has focused primarily upon the therapeutic potential of corticosteroids and NSAIDs. Although beneficial, the use of systemic corticosteroids is limited by their unacceptable adverse effects. It is unclear if inhaled corticosteroids are a viable alternative, although their use in CF has dramatically increased in recent years. High-dose ibuprofen has been shown to slow progression of CF lung disease, but its use has not been widely adopted despite a favorable risk-benefit profile. Thus, other anti-inflammatory approaches are under investigation. Since the inflammatory response can be triggered by many stimuli and since the pathways activated by these stimuli produce many mediators, there are a plethora of targets for anti-inflammatory therapeutics. Specific antibodies, receptor antagonists, and counter-regulatory cytokines, such as interleukin (IL)-10 and interferon-γ, inhibit the pro-inflammatory mediators responsible for the damaging inflammation in the CF airway, including tumor necrosis factor-α, IL-1β and IL-8. Studies of molecules that modulate intracellular signaling cascades that lead to the production of inflammatory mediators, are underway in CF. For patients with established disease, recent and projected advances in therapies that are directed at neutrophil products, such as DNase, antioxidants, and protease inhibitors, hold great promise for limiting the consequences of the inflammatory response. To optimize anti-inflammatory therapy, it is necessary to understand the mechanism of action of these agents in the CF lung to determine which agents will be most beneficial, and to determine which therapies should be initiated at what age and stage of lung disease. Hope remains that correction of the abnormal CF transmembrane conductance regulator protein or gene replacement therapy will be curative. However, correction of the basic defect must also correct the dysregulated inflammatory response in order to be effective. Until those therapies aimed at repairing the basic defect are realized, limiting the effects of the inflammatory process will be important in slowing the decline in lung function and thus prolonging survival in patients with CF.

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Acknowledgments

Grant support from the National Institutes of Health Grant P30-DK27651 and the US Cystic Fibrosis Foundation is gratefully acknowledged.

James F. Chmiel has no conflicts of interest that are directly relevant to the contents of this manuscript.

Michael W. Konstan serves, or has served, as an advisor or consultant for Bayer, Boehringer-Ingelheim, Chiron, Debiopharma and Genentech.

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  1. Division of Pediatric Pulmonology, MS# 6006, Rainbow Babies and Children’s Hospital, 11100 Euclid Avenue, Cleveland, Ohio, 44106, USA

    James F. Chmiel & Michael W. Konstan

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  1. James F. Chmiel
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Chmiel, J.F., Konstan, M.W. Anti-Inflammatory Medications for Cystic Fibrosis Lung Disease. Treat Respir Med 4, 255–273 (2005). https://doi.org/10.2165/00151829-200504040-00004

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