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Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis

Science  15 Aug 2014:
Vol. 345, Issue 6198, pp. 818-822
DOI: 10.1126/science.1255825

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A breathtaking tale of sticky mucus

Patients with cystic fibrosis have difficulty breathing because their airways are clogged with thick mucus. Does this mucus accumulate because there is a defect in the way it is produced? Or does it accumulate because of other disease features, such as dehydration or airway wall remodeling? Distinguishing between these possibilities is important for future drug development. In a study of piglets with cystic fibrosis, Hoegger et al. identify mucus production as the primary defect (see the Perspective by Wine). The airway glands of the piglets synthesized strands of mucus normally, but the strands were never released and stayed tethered to the gland ducts.

Science, this issue p. 818; see also p. 730

Abstract

Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment.

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