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There are currently alternative hypotheses that attempt to describe the abnormally viscous and elastic mucus that is a hallmark of CF airways disease, including: 1) loss of CF transmembrane regulator (CFTR)-dependent airway surface volume (water) secretion, producing mucus hyperconcentration-dependent increased viscosity, and 2) impaired bicarbonate secretion by CFTR, producing acidification of airway surfaces and increased mucus viscosity.<\/jats:p><jats:p>A series of experiments was conducted to determine the contributions of mucus concentration<jats:italic>versus<\/jats:italic>pH to the rheological properties of airway mucus across length scales from the nanoscopic to macroscopic.<\/jats:p><jats:p>For length scales greater than the nanoscopic,<jats:italic>i.e.<\/jats:italic>those relevant to mucociliary clearance, the effect of mucus concentration dominated over the effect of airway acidification.<\/jats:p><jats:p>Mucus hydration and chemical reduction of disulfide bonds that connect mucin monomers are more promising therapeutic approaches than alkalisation.<\/jats:p>","DOI":"10.1183\/13993003.01297-2018","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T17:27:58Z","timestamp":1540488478000},"page":"1801297","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":139,"title":["Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH"],"prefix":"10.1183","volume":"52","author":[{"given":"David B.","family":"Hill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Kissner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyad","family":"Atieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian\u00a0C.","family":"Garbarine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Markovetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Christy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Habibpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Tarran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-4456","authenticated-orcid":false,"given":"M. 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