Editorial New England Journal of Medicine

Editorial New England Journal of Medicine - editorials...

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editorials n engl j med 354;3 www.nejm.org january 19, 2006 293 ministered by inhalation, deposition will prefer- entially occur in areas not obstructed by plugs of mucus. The most affected areas may therefore not benefit from this treatment approach. The veri- fication of this hypothesis would support the early use of such drugs in cystic fibrosis before mucus can accumulate extensively in the lung. More- over, hypertonic droplets undergo hygroscopic growth in a water-vapor–saturated environment such as the respiratory tract — a factor that will increase the size of the particles during inhala- tion and favor a more central deposition. 8 This finding makes it less likely that an adequate amount of the substance will enter the smaller airways, the area where cystic fibrosis lung dis- ease is thought to originate. In addition, the small airways have an overall surface area that far ex- ceeds the surface area of the central airways. It is not clear what quantity of an osmotic active agent is needed for the complete restoration of airway surface liquid in the small airways of pa- tients with cystic fibrosis. Unless nebulizers could specifically target this area of the bronchial tree, the feasibility of this approach may potentially be limited by the amount of fluid that can safely be delivered through the larger airways. There- fore, pharmacologic intervention with a direct effect on chloride secretion, on sodium hyperab- sorption, or both may ultimately be more effective in restoring the volume of airway surface liquid. In the meantime, hypertonic saline offers a new treatment strategy for patients and brings us clos- er to targeting the underlying abnormality, rath- er than the consequences of defective mucociliary clearance. No potential conflict of interest relevant to this article was reported. From the Hospital for Sick Children and the University of Toronto, Toronto. Mall M, Grubb BR, Harkema JR, O’Neal WK, Boucher RC. Increased airway epithelial Na+ absorption produces cystic fi- brosis-like lung disease in mice. Nat Med 2004;10:487-93. Wark PA, McDonald V, Jones AP. Nebulised hypertonic sa- line for cystic fibrosis. Cochrane Database Syst Rev 2005;3: CD001506. Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fi- brosis with hypertonic saline. N Engl J Med 2006;354:241-50. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fi- brosis. N Engl J Med 2006;354:229-40. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent adminis- tration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999;340:23-30. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of
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Editorial New England Journal of Medicine - editorials...

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