Treatment of airway inflammation in cystic fibrosis.
Airway inflammation is now recognized as a major factor in the pathogenesis of cystic fibrosis (CF) lung disease. Therapies aimed at decreasing the inflammatory response represent a new strategy for treatment, and attention has focused primarily on the therapeutic potential of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). Alternate-day prednisone (1 mg/kg) may be beneficial; however, unacceptable adverse effects limit long-term use. Inhaled corticosteroids are under investigation as a safer alternative. High-dose ibuprofen (approximately 20-30 mg/kg twice daily) has been shown to decrease the progression of CF lung disease, particularly in children with mild lung disease, and it is without significant toxicity. Other NSAIDs (piroxicam) are under consideration, as well as pentoxifylline and fish oil. The rationale for all of these agents lies in their potential to decrease neutrophil influx into the lung. Because of the large burden and deleterious effects of uninhibited neutrophil elastase and oxidants in the CF airway, antiproteases and antioxidants are also being studied. To optimize anti-inflammatory therapy, it is necessary to understand the mechanism of action of these agents in the CF lung, to determine which of these agents would provide the most benefit to patients with CF, and to determine which therapies should be initiated at what age or stage of lung disease. It is hoped that adding anti-inflammatory therapy to an already comprehensive treatment program will decrease morbidity and improve the quality of life for patients with CF.
Konstan
M W
MW
Pediatric Pulmonary Division, Rainbow Babies and Childrens Hospital, Cleveland, OH 44106, USA.
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000367:Age Factors; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy*; D018450:Disease Progression; D005395:Fish Oils / Q000627:therapeutic use; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use; D007249:Inflammation; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010431:Pentoxifylline / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010894:Piroxicam / Q000008:administration & dosage / Q000627:therapeutic use; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D011788:Quality of Life
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005395:Fish Oils; D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011480:Protease Inhibitors; D010894:Piroxicam; D019272:Leukocyte Elastase; D010431:Pentoxifylline; D011241:Prednisone; D007052:Ibuprofen