Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, Raymond WW, Lachowicz-Scroggins ME, Di Maio S, Hoffman EA, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018;128:997–1009.
Article
PubMed
PubMed Central
Google Scholar
Burgel PR, Montani D, Danel C, Dusser DJ, Nadel JA. A morphometric study of mucins and small airway plugging in cystic fibrosis. Thorax. 2007;62:153–61.
Article
PubMed
Google Scholar
Williams OW, Sharafkhaneh A, Kim V, Dickey BF, Evans CM. Airway mucus: from production to secretion. Am J Respir Cell Mol Biol. 2006;34:527–36.
Article
CAS
PubMed
PubMed Central
Google Scholar
Turkovic L, Caudri D, Rosenow T, Hall G, Stick S. Presence of mucus plugging is predictive of long term lung function in children with cystic fibrosis. Eur Respir J. 2017;50:OA4401.
Google Scholar
Widdicombe JH. Regulation of the depth and composition of airway surface liquid. J Anat. 2002;201:313–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tarran R. Regulation of airway surface liquid volume and mucus transport by active ion transport. Proc Am Thorac Soc. 2004;1:42–6.
Article
CAS
PubMed
Google Scholar
Ma J, Rubin BK, Voynow JA: Mucins, Mucus, and Goblet Cells. Chest 2017.
Webster MJ, Tarran R: Chapter Nine - Slippery When Wet: Airway Surface Liquid Homeostasis and Mucus Hydration. In Current Topics in Membranes. Volume 81. Edited by Levitane I, Delpire E, Rasgado-Flores H: Academic Press; 2018: 293–335.
Wu DX, Lee CY, Uyekubo SN, Choi HK, Bastacky SJ, Widdicombe JH. Regulation of the depth of surface liquid in bovine trachea. Am J Phys. 1998;274:L388–95.
CAS
Google Scholar
Kreda SM, Okada SF, van Heusden CA, O'Neal W, Gabriel S, Abdullah L, Davis CW, Boucher RC, Lazarowski ER. Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells. J Physiol. 2007;584:245–59.
Article
CAS
PubMed
PubMed Central
Google Scholar
Plasschaert LW, Zilionis R, Choo-Wing R, Savova V, Knehr J, Roma G, Klein AM, Jaffe AB. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature. 2018;560:377–81.
Article
CAS
PubMed
PubMed Central
Google Scholar
Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, Yuan F, Chen S, Leung HM, Villoria J, et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018;560:319–24.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tang XX, Ostedgaard LS, Hoegger MJ, Moninger TO, Karp PH, McMenimen JD, Choudhury B, Varki A, Stoltz DA, Welsh MJ. Acidic pH increases airway surface liquid viscosity in cystic fibrosis. J Clin Invest. 2016;126:879–91.
Article
PubMed
PubMed Central
Google Scholar
Bansil R, Turner BS. The biology of mucus: composition, synthesis and organization. Adv Drug Deliv Rev. 2018;124:3–15.
Article
CAS
PubMed
Google Scholar
Gum JR. Mucin genes and the proteins they encode: structure, diversity, and regulation. Am J Respir Cell Mol Biol. 1992;7:557–64.
Article
CAS
PubMed
Google Scholar
Dhanisha SS, Guruvayoorappan C, Drishya S, Abeesh P. Mucins: structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets. Crit Rev Oncol Hematol. 2018;122:98–122.
Article
PubMed
Google Scholar
Thornton DJ, Sheehan JK, Carlstedt I. Heterogeneity of mucus glycoproteins from cystic fibrotic sputum. Are there different families of mucins? Biochem J. 1991;276(Pt 3):677–82.
Article
CAS
PubMed
PubMed Central
Google Scholar
Boucher RC, Cotton CU, Gatzy JT, Knowles MR, Yankaskas JR. Evidence for reduced cl- and increased Na+ permeability in cystic fibrosis human primary cell cultures. J Physiol. 1988;405:77–103.
Article
CAS
PubMed
PubMed Central
Google Scholar
Quinton PM. Role of epithelial HCO3(−) transport in mucin secretion: lessons from cystic fibrosis. Am J Physiol Cell Physiol. 2010;299:C1222–33.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, et al. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science. 2014;345:818–22.
Article
CAS
PubMed
PubMed Central
Google Scholar
Henke MO, John G, Germann M, Lindemann H, Rubin BK. MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation. Am J Respir Crit Care Med. 2007;175:816–21.
Article
CAS
PubMed
Google Scholar
Christenson SA, van den Berge M, Faiz A, Inkamp K, Bhakta N, Bonser LR, Zlock LT, Barjaktarevic IZ, Barr RG, Bleecker ER, et al. An airway epithelial IL-17A response signature identifies a steroid-unresponsive COPD patient subgroup. J Clin Invest. 2019;129:169–81.
Article
PubMed
Google Scholar
Kesimer M, Ford AA, Ceppe A, Radicioni G, Cao R, Davis CW, Doerschuk CM, Alexis NE, Anderson WH, Henderson AG, et al. Airway Mucin concentration as a marker of chronic bronchitis. N Engl J Med. 2017;377:911–22.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lai T, Wu D, Chen M, Cao C, Jing Z, Huang L, Lv Y, Zhao X, Lv Q, Wang Y, et al. YKL-40 expression in chronic obstructive pulmonary disease: relation to acute exacerbations and airway remodeling. Respir Res. 2016;17:31.
Article
CAS
PubMed
PubMed Central
Google Scholar
Saetta M, Turato G, Baraldo S, Zanin A, Braccioni F, Mapp CE, Maestrelli P, Cavallesco G, Papi A, Fabbri LM. Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med. 2000;161:1016–21.
Article
CAS
PubMed
Google Scholar
Dransfield MT, Wilhelm AM, Flanagan B, Courville C, Tidwell SL, Raju SV, Gaggar A, Steele C, Tang LP, Liu B, Rowe SM. Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD. Chest. 2013;144:498–506.
Article
CAS
PubMed
PubMed Central
Google Scholar
Verdugo P. Supramolecular dynamics of mucus. Cold Spring Harb Perspect Med. 2012;2.
Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol. 1995;57:607–34.
Article
CAS
PubMed
Google Scholar
Verdugo P. Goblet cells secretion and mucogenesis. Annu Rev Physiol. 1990;52:157–76.
Article
CAS
PubMed
Google Scholar
Thornton DJ, Rousseau K, McGuckin MA. Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol. 2008;70:459–86.
Article
CAS
PubMed
Google Scholar
Kesimer M, Makhov AM, Griffith JD, Verdugo P, Sheehan JK. Unpacking a gel-forming mucin: a view of MUC5B organization after granular release. Am J Physiol Lung Cell Mol Physiol. 2010;298:L15–22.
Article
CAS
PubMed
Google Scholar
Ermund A, Trillo-Muyo S, Hansson GC. Assembly, release, and transport of airway Mucins in pigs and humans. Annals of the American Thoracic Society. 2018;15:S159–63.
Article
PubMed
PubMed Central
Google Scholar
Evans CM, Kim K, Tuvim MJ, Dickey BF. Mucus hypersecretion in asthma: causes and effects. Curr Opin Pulm Med. 2009;15:4–11.
Article
CAS
PubMed
PubMed Central
Google Scholar
Copin MC, Buisine MP, Devisme L, Leroy X, Escande F, Gosselin B, Aubert JP, Porchet N. Normal respiratory mucosa, precursor lesions and lung carcinomas: differential expression of human mucin genes. Front Biosci. 2001;6:D1264–75.
Article
CAS
PubMed
Google Scholar
Hovenberg HW, Davies JR, Herrmann A, Lindén CJ, Carlstedt I. MUC5AC, but not MUC2, is a prominent mucin in respiratory secretions. Glycoconj J. 1996;13:839–47.
Article
CAS
PubMed
Google Scholar
Zhu L, Lee P, Yu D, Tao S, Chen Y. Cloning and characterization of human MUC19 gene. Am J Respir Cell Mol Biol. 2011;45:348–58.
Article
CAS
PubMed
Google Scholar
Chen Y, Zhao YH, Kalaslavadi TB, Hamati E, Nehrke K, Le AD, Ann DK, Wu R. Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues. Am J Respir Cell Mol Biol. 2004;30:155–65.
Article
CAS
PubMed
Google Scholar
Vieira VG, Prolla JC. Clinical evaluation of eosinophils in the sputum. J Clin Pathol. 1979;32:1054–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Thompson AB, Bohling T, Payvandi F, Rennard SI. Lower respiratory tract lactoferrin and lysozyme arise primarily in the airways and are elevated in association with chronic bronchitis. J Lab Clin Med. 1990;115:148–58.
CAS
PubMed
Google Scholar
Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033–9.
Article
CAS
PubMed
Google Scholar
Petsky HL, Cates CJ, Kew KM, Chang AB. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis. Thorax. 2018;73:1110–9.
Article
PubMed
Google Scholar
Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, Wenzel SE, Peters SP, Meyers DA, Bleecker ER, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol. 2014;133:1557–63 e1555.
Article
PubMed
Google Scholar
Margaroli C, Garratt LW, Horati H, Dittrich AS, Rosenow T, Montgomery ST, Frey DL, Brown MR, Schultz C, Guglani L, et al. Elastase exocytosis by airway neutrophils is associated with early lung damage in children with cystic fibrosis. Am J Respir Crit Care Med. 2019;199:873–81.
Article
CAS
PubMed
PubMed Central
Google Scholar
Heron M, Grutters JC, ten Dam-Molenkamp KM, Hijdra D, van Heugten-Roeling A, Claessen AM, Ruven HJ, van den Bosch JM, van Velzen-Blad H. Bronchoalveolar lavage cell pattern from healthy human lung. Clin Exp Immunol. 2012;167:523–31.
Article
CAS
PubMed
PubMed Central
Google Scholar
Guiedem E, Ikomey GM, Nkenfou C, Walter PE, Mesembe M, Chegou NN, Jacobs GB, Okomo Assoumou MC. Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD. BMC Res Notes. 2018;11:192.
Article
CAS
PubMed
PubMed Central
Google Scholar
Potter JL, Spector S, Matthews LW, Lemm J. Studies on pulmonary secretions. 3. The nucleic acids in whole pulmonary secretions from patients with cystic fibrosis, bronchiectasis, and laryngectomy. Am Rev Respir Dis. 1969;99:909–16.
CAS
PubMed
Google Scholar
Neeli I, Khan SN, Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol. 2008;180:1895–902.
Article
CAS
PubMed
Google Scholar
Efthimiadis A, Spanevello A, Hamid Q, Kelly MM, Linden M, Louis R, Pizzichini MMM, Pizzichini E, Ronchi C, Van Overveld F, Djukanovic R. Methods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation. Eur Respir J. 2002;20:19s–23s.
Article
Google Scholar
Jackson A, Kemp P, Giddings J, Sugar R. Development and validation of a lectin-based assay for the quantitation of rat respiratory mucin. Novartis Found Symp. 2002;248:94–112.
CAS
PubMed
Google Scholar
Hilgers J, von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P. Quantitation of polymorphic epithelial mucin: a challenge for biochemists and immunologists. Scand J Clin Lab Invest Suppl. 1995;221:81–6.
Article
CAS
PubMed
Google Scholar
Rose MC, Piazza FM, Chen YA, Alimam MZ, Bautista MV, Letwin N, Rajput B. Model systems for investigating mucin gene expression in airway diseases. J Aerosol Med. 2000;13:245–61.
Article
CAS
PubMed
Google Scholar
Wine JJ. Parasympathetic control of airway submucosal glands: central reflexes and the airway intrinsic nervous system. Auton Neurosci. 2007;133:35–54.
Article
PubMed
PubMed Central
Google Scholar
Reznikov LR, Liao YSJ, Gu T, Davis KM, Kuan SP, Atanasova KR, Dadural JS, Collins EN, Guevara MV, Vogt K. Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid. Am J Physiol Lung Cell Mol Physiol. 2019;316:L131–43.
Article
CAS
PubMed
Google Scholar
Mall MA. Unplugging mucus in cystic fibrosis and chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016;13(Suppl 2):S177–85.
PubMed
Google Scholar
Cho HJ, Joo NS, Wine JJ. Mucus secretion from individual submucosal glands of the ferret trachea. Am J Physiol Lung Cell Mol Physiol. 2010;299:L124–36.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ohtsuka R, Doi K, Itagaki S. Histological characteristics of respiratory system in Brown Norway rat. Exp Anim. 1997;46:127–33.
Article
CAS
PubMed
Google Scholar
Desseyn JL, Aubert JP, Porchet N, Laine A. Evolution of the large secreted gel-forming mucins. Mol Biol Evol. 2000;17:1175–84.
Article
CAS
PubMed
Google Scholar
Fogg FJJ, Hutton DA, Jumel K, Pearson JP, Harding SE, Allen A. Characterization of pig colonic mucins. Biochem J. 1996;316:937–42.
Article
CAS
PubMed
PubMed Central
Google Scholar
Padra M, Adamczyk B, Benktander J, Flahou B, Skoog EC, Padra JT, Smet A, Jin CS, Ducatelle R, Samuelsson T, et al. Helicobacter suis binding to carbohydrates on human and porcine gastric mucins and glycolipids occurs via two modes. Virulence. 2018;9:898–918.
Article
CAS
PubMed
PubMed Central
Google Scholar
Takeyama K, Jung B, Shim JJ, Burgel PR, Dao-Pick T, Ueki IF, Protin U, Kroschel P, Nadel JA. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol. 2001;280:L165–72.
Article
CAS
PubMed
Google Scholar
Jeffries JL, Jia J, Choi W, Choe S, Miao J, Xu Y, Powell R, Lin J, Kuang Z, Gaskins HR, Lau GW. Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis(x) to increase binding to airway epithelial cells. Mucosal Immunol. 2016;9:1039–50.
Article
CAS
PubMed
Google Scholar
Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med. 2010;363:2233–47.
Article
CAS
PubMed
PubMed Central
Google Scholar
Davis CW. Regulation of mucin secretion from in vitro cellular models. Novartis Found Symp. 2002;248:113–25 discussion 125–131, 277–182.
CAS
PubMed
Google Scholar
Kemp PA, Sugar RA, Jackson AD. Nucleotide-mediated mucin secretion from differentiated human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2004;31:446–55.
Article
CAS
PubMed
Google Scholar
Abdullah LH, Wolber C, Kesimer M, Sheehan JK, Davis CW. Studying mucin secretion from human bronchial epithelial cell primary cultures. Methods Mol Biol. 2012;842:259–77.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kesimer M, Kirkham S, Pickles RJ, Henderson AG, Alexis NE, Demaria G, Knight D, Thornton DJ, Sheehan JK. Tracheobronchial air-liquid interface cell culture: a model for innate mucosal defense of the upper airways? Am J Physiol Lung Cell Mol Physiol. 2009;296:L92–L100.
Article
CAS
PubMed
Google Scholar
Weynants P, Cordier JF, Cellier CC, Pages J, Loire R, Brune J. Primary immunocytoma of the lung: the diagnostic value of bronchoalveolar lavage. Thorax. 1985;40:542–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
Andreasson AS, Karamanou DM, Gillespie CS, Ozalp F, Butt T, Hill P, Jiwa K, Walden HR, Green NJ, Borthwick LA, et al. Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion. Eur J Cardiothorac Surg. 2017;51:577–86.
PubMed
Google Scholar
Reynolds HY, Newball HH. Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage. J Lab Clin Med. 1974;84:559–73.
CAS
PubMed
Google Scholar
Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Report of the European Society of Pneumology Task Group. Eur Respir J. 1989;2:561–85.
Google Scholar
Leaker BR, Nicholson GC, Ali FY, Daudi N, O'Connor BJ, Barnes PJ. Bronchoabsorption; a novel bronchoscopic technique to improve biomarker sampling of the airway. Respir Res. 2015;16:102.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bartoli ML, Bacci E, Carnevali S, Cianchetti S, Dente FL, Di Franco A, Giannini D, Taccola M, Vagaggini B, Paggiaro PL. Quality evaluation of samples obtained by spontaneous or induced sputum: comparison between two methods of processing and relationship with clinical and functional findings. J Asthma. 2002;39:479–86.
Article
CAS
PubMed
Google Scholar
Weiszhar Z, Horvath I. Induced sputum analysis: step by step. Breathe. 2013;9:300–6.
Article
Google Scholar
in’t Veen JC, de Gouw HW, Smits HH, Sont JK, Hiemstra PS, Sterk PJ, Bel EH. Repeatability of cellular and soluble markers of inflammation in induced sputum from patients with asthma. Eur Respir J. 1996;9:2441–7.
Article
Google Scholar
Pizzichini MM, Popov TA, Efthimiadis A, Hussack P, Evans S, Pizzichini E, Dolovich J, Hargreave FE. Spontaneous and induced sputum to measure indices of airway inflammation in asthma. Am J Respir Crit Care Med. 1996;154:866–9.
Article
CAS
PubMed
Google Scholar
Hall GJ, Gandevia B. Relationship of the loose cough sign to daily sputum volume. Observer variation in its detection. Br J Prev Soc Med. 1971;25:109–13.
CAS
PubMed
PubMed Central
Google Scholar
Kamin W, Klar-Hlawatsch B, Truebel H. Easy removal of a large mucus plug with a flexible paediatric bronchoscope after administration of rhDNase (Pulmozyme). Klin Padiatr. 2006;218:88–91.
Article
CAS
PubMed
Google Scholar
Berra L, Coppadoro A, Bittner EA, Kolobow T, Laquerriere P, Pohlmann JR, Bramati S, Moss J, Pesenti A. A clinical assessment of the mucus shaver: a device to keep the endotracheal tube free from secretions. Crit Care Med. 2012;40:119–24.
Article
PubMed
PubMed Central
Google Scholar
Li Bassi G, Zanella A, Cressoni M, Stylianou M, Kolobow T. Following tracheal intubation, mucus flow is reversed in the semirecumbent position: possible role in the pathogenesis of ventilator-associated pneumonia. Crit Care Med. 2008;36:518–25.
Article
PubMed
Google Scholar
Rubin BK, Ramirez O, Zayas JG, Finegan B, King M. Collection and analysis of respiratory mucus from subjects without lung disease. Am Rev Respir Dis. 1990;141:1040–3.
Article
CAS
PubMed
Google Scholar
Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, Mandal S, Martin J, Mills J, Navani N, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013;68(Suppl 1):i1–i44.
Article
PubMed
Google Scholar
Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, Kuebler WM. Acute lung injury in animals study G: an official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44:725–38.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vieira MO, Pizzichini E, Steidle LJ, da Silva JK, Pizzichini MM. Sputum induction in severe exacerbations of asthma: safety of a modified method. Eur Respir J. 2011;38:979–80.
Article
CAS
PubMed
Google Scholar
Sagel SD, Chmiel JF, Konstan MW. Sputum biomarkers of inflammation in cystic fibrosis lung disease. Proc Am Thorac Soc. 2007;4:406–17.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lapinsky SE. Endotracheal intubation in the ICU. Crit Care. 2015;19:258.
Article
PubMed
PubMed Central
Google Scholar
Mietto C, Foley K, Salerno L, Oleksak J, Pinciroli R, Goverman J, Berra L. Removal of endotracheal tube obstruction with a secretion clearance device. Respir Care. 2014;59:e122–6.
Article
PubMed
Google Scholar
Khelloufi M-K, Loiseau E, Jaeger M, Molinari N, Chanez P, Gras D, Viallat A. Spatiotemporal organization of cilia drives multiscale mucus swirls in model human bronchial epithelium. Sci Rep. 2018;8:2447.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hill DB, Vasquez PA, Mellnik J, McKinley SA, Vose A, Mu F, Henderson AG, Donaldson SH, Alexis NE, Boucher RC, Forest MG. A biophysical basis for mucus solids concentration as a candidate biomarker for airways disease. PLoS One. 2014;9:e87681.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ehre C, Worthington EN, Liesman RM, Grubb BR, Barbier D, O’Neal WK, Sallenave J-M, Pickles RJ, Boucher RC. Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs. Proc Natl Acad Sci. 2012;109:16528–33.
Article
PubMed
PubMed Central
Google Scholar
Ermund A, Meiss LN, Rodriguez-Pineiro AM, Bahr A, Nilsson HE, Trillo-Muyo S, Ridley C, Thornton DJ, Wine JJ, Hebert H, et al. The normal trachea is cleaned by MUC5B mucin bundles from the submucosal glands coated with the MUC5AC mucin. Biochem Biophys Res Commun. 2017;492:331–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rogers TD, Ostrowski LE, Livraghi-Butrico A, Button B, Grubb BR. Mucociliary clearance in mice measured by tracking trans-tracheal fluorescence of nasally aerosolized beads. Sci Rep. 2018;8:14744.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ostedgaard LS, Moninger TO, McMenimen JD, Sawin NM, Parker CP, Thornell IM, Powers LS, Gansemer ND, Bouzek DC, Cook DP, et al. Gel-forming mucins form distinct morphologic structures in airways. Proc Natl Acad Sci U S A. 2017;114:6842–7.
CAS
PubMed
PubMed Central
Google Scholar
Meyerholz DK, Lambertz AM, Reznikov LR, Ofori-Amanfo GK, Karp PH, McCray PB Jr, Welsh MJ, Stoltz DA. Immunohistochemical detection of markers for translational studies of lung disease in pigs and humans. Toxicol Pathol. 2016;44:434–41.
Article
CAS
PubMed
Google Scholar
Rose MC, Voter WA, Brown CF, Kaufman B. Structural features of human tracheobronchial mucus glycoprotein. Biochem J. 1984;222:371–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Birket SE, Davis JM, Fernandez CM, Tuggle KL, Oden AM, Chu KK, Tearney GJ, Fanucchi MV, Sorscher EJ, Rowe SM. Development of an airway mucus defect in the cystic fibrosis rat. JCI Insight. 2018;3.
Donnelley M, Morgan KS, Awadalla M, Farrow NR, Hall C, Parsons DW. High-resolution mucociliary transport measurement in live excised large animal trachea using synchrotron X-ray imaging. Respir Res. 2017;18:95.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gradl R, Dierolf M, Günther B, Hehn L, Möller W, Kutschke D, Yang L, Donnelley M, Murrie R, Erl A, et al. In vivo dynamic phase-contrast X-ray imaging using a compact light source. Sci Rep. 2018;8:6788.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ramsey KA, Rosenow T, Turkovic L, Skoric B, Banton G, Adams AM, Simpson SJ, Murray C, Ranganathan SC, Stick SM, Hall GL. Lung clearance index and structural lung disease on computed tomography in early cystic fibrosis. Am J Respir Crit Care Med. 2016;193:60–7.
Article
PubMed
Google Scholar
Kang JW, Lee YH, Kang MJ, Lee HJ, Oh R, Min HJ, Namkung W, Choi JY, Lee SN, Kim CH, et al. Synergistic mucus secretion by histamine and IL-4 through TMEM16A in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2017;313:L466–76.
Article
PubMed
Google Scholar
Thornton DJ, Carlstedt I, Howard M, Devine PL, Price MR, Sheehan JK. Respiratory mucins: identification of core proteins and glycoforms. Biochem J. 1996;316(Pt 3):967–75.
Article
CAS
PubMed
PubMed Central
Google Scholar
McGuckin MA, Thornton DJ. Detection and quantitation of mucins using chemical, lectin, and antibody methods. Methods Mol Biol. 2000;125:45–55.
CAS
PubMed
Google Scholar
Taylor CR, Levenson RM. Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006;49:411–24.
Article
CAS
PubMed
Google Scholar
Walker RA. Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment I. Histopathology. 2006;49:406–10.
Article
CAS
PubMed
Google Scholar
Meyerholz DK, Beck AP. Principles and approaches for reproducible scoring of tissue stains in research. Lab Investig. 2018;98:844–55.
Article
PubMed
Google Scholar
Waters JC. Accuracy and precision in quantitative fluorescence microscopy. J Cell Biol. 2009;185:1135–48.
Article
CAS
PubMed
PubMed Central
Google Scholar
Meyerholz DK, Beck AP. Fundamental concepts for Semiquantitative tissue scoring in translational research. ILAR J. 2019.
Button B, Cai LH, Ehre C, Kesimer M, Hill DB, Sheehan JK, Boucher RC, Rubinstein M. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science. 2012;337:937–41.
Article
CAS
PubMed
PubMed Central
Google Scholar
Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002;33:293–306.
Article
PubMed
Google Scholar
Foster WM, Walters DM, Longphre M, Macri K, Miller LM. Methodology for the measurement of mucociliary function in the mouse by scintigraphy. J Appl Physiol (1985). 2001;90:1111–7.
Zuhdi Alimam M, Piazza FM, Selby DM, Letwin N, Huang L, Rose MC. Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways. Am J Respir Cell Mol Biol. 2000;22:253–60.
Article
CAS
PubMed
Google Scholar
Chen Y, Nickola TJ, DiFronzo NL, Colberg-Poley AM, Rose MC. Dexamethasone-mediated repression of MUC5AC gene expression in human lung epithelial cells. Am J Respir Cell Mol Biol. 2006;34:338–47.
Article
CAS
PubMed
Google Scholar
Rousseau K, Kirkham S, McKane S, Newton R, Clegg P, Thornton DJ. Muc5b and Muc5ac are the major oligomeric mucins in equine airway mucus. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1396–404.
Article
CAS
PubMed
Google Scholar
Chen Y, Watson AM, Williamson CD, Rahimi M, Liang C, Colberg-Poley AM, Rose MC. Glucocorticoid receptor and histone deacetylase-2 mediate dexamethasone-induced repression of MUC5AC gene expression. Am J Respir Cell Mol Biol. 2012;47:637–44.
Article
CAS
PubMed
PubMed Central
Google Scholar
Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, et al. Muc5b is required for airway defence. Nature. 2014;505:412–6.
Article
CAS
PubMed
Google Scholar
Evans CM, Raclawska DS, Ttofali F, Liptzin DR, Fletcher AA, Harper DN, McGing MA, McElwee MM, Williams OW, Sanchez E, et al. The polymeric mucin Muc5ac is required for allergic airway hyperreactivity. Nat Commun. 2015;6:6281.
Article
CAS
PubMed
Google Scholar
Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, Dang H, et al. Localization of secretory Mucins MUC5AC and MUC5B in Normal/healthy human airways. Am J Respir Crit Care Med. 2019;199:715–27.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lin H, Carlson DM, St George JA, Plopper CG, Wu R. An ELISA method for the quantitation of tracheal mucins from human and nonhuman primates. Am J Respir Cell Mol Biol. 1989;1:41–8.
Article
CAS
PubMed
Google Scholar
Yang PC, Luh KT, Kuo SH, Wu CW. Immunocytochemistry and ELISA quantitation of mucin for diagnosis of malignant pleural effusions. Am Rev Respir Dis. 1992;146:1571–5.
Article
CAS
PubMed
Google Scholar
Ramsey KA, Rushton ZL, Ehre C. Mucin Agarose gel electrophoresis: Western blotting for high-molecular-weight glycoproteins. J Vis Exp. 2016.
Thornton DJ, Holmes DF, Sheehan JK, Carlstedt I. Quantitation of mucus glycoproteins blotted onto nitrocellulose membranes. Anal Biochem. 1989;182:160–4.
Article
CAS
PubMed
Google Scholar
Bamrungphon W, Prempracha N, Bunchu N, Rangdaeng S, Sandhu T, Srisukho S, Boonla C, Wongkham S. A new mucin antibody/enzyme-linked lectin-sandwich assay of serum MUC5AC mucin for the diagnosis of cholangiocarcinoma. Cancer Lett. 2007;247:301–8.
Article
CAS
PubMed
Google Scholar
Sakamoto S, Putalun W, Vimolmangkang S, Phoolcharoen W, Shoyama Y, Tanaka H, Morimoto S. Enzyme-linked immunosorbent assay for the quantitative/qualitative analysis of plant secondary metabolites. J Nat Med. 2018;72:32–42.
Article
CAS
PubMed
Google Scholar
Gull I, Wirth M, Gabor F. Development of a sensitive and reliable ELISA for quantification of wheat germ agglutinin. J Immunol Methods. 2007;318:20–9.
Article
CAS
PubMed
Google Scholar
Ali M, Lillehoj EP, Park Y, Kyo Y, Kim KC. Analysis of the proteome of human airway epithelial secretions. Proteome Sci. 2011;9.
Nicholas B, Skipp P, Mould R, Rennard S, Davies DE, O'Connor CD, Djukanovic R. Shotgun proteomic analysis of human-induced sputum. Proteomics. 2006;6:4390–401.
Article
CAS
PubMed
Google Scholar
Radicioni G, Cao R, Carpenter J, Ford AA, Wang TT, Li Y, Kesimer M. The innate immune properties of airway mucosal surfaces are regulated by dynamic interactions between mucins and interacting proteins: the mucin interactome. Mucosal Immunol. 2016;9:1442–54.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kesimer M, Sheehan JK. Mass spectrometric analysis of mucin core proteins. Methods Mol Biol. 2012;842:67–79.
Article
CAS
PubMed
PubMed Central
Google Scholar
Stahl GH, Ellis DB: Biosynthesis of respiratory-tract mucins. A comparison of canine epithelial goblet-cell and submucosal-gland secretions. Biochem J 1973, 136:845–850.
Ellis DB, Stahl GH. Biosynthesis of respiratory-tract mucins. Incorporation of radioactive precursors into glycoproteins by canine tracheal explants in vitro. Biochem J. 1973;136:837–44.
CAS
PubMed
PubMed Central
Google Scholar
Rose MC, Lynn WS, Kaufman B. Resolution of the major components of human lung mucosal gel and their capabilities for reaggregation and gel formation. Biochemistry. 1979;18:4030–7.
Article
CAS
PubMed
Google Scholar
Svartengren K, Wiman LG, Thyberg P, Rigler R. Laser light scattering spectroscopy: a new method to measure tracheobronchial mucociliary activity. Thorax. 1989;44:539–47.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sheehan JK, Carlstedt I. Hydrodynamic properties of human cervical-mucus glycoproteins in 6M-guanidinium chloride. Biochem J. 1984;217:93–101.
Article
CAS
PubMed
PubMed Central
Google Scholar
Shah VS, Meyerholz DK, Tang XX, Reznikov L, Abou Alaiwa M, Ernst SE, Karp PH, Wohlford-Lenane CL, Heilmann KP, Leidinger MR, et al. Airway acidification initiates host defense abnormalities in cystic fibrosis mice. Science. 2016;351:503–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Derichs N, Jin BJ, Song Y, Finkbeiner WE, Verkman AS. Hyperviscous airway periciliary and mucous liquid layers in cystic fibrosis measured by confocal fluorescence photobleaching. FASEB J. 2011;25:2325–32.
Article
CAS
PubMed
PubMed Central
Google Scholar
Birket SE, Chu KK, Liu L, Houser GH, Diephuis BJ, Wilsterman EJ, Dierksen G, Mazur M, Shastry S, Li Y, et al. A functional anatomic defect of the cystic fibrosis airway. Am J Respir Crit Care Med. 2014;190:421–32.
Article
PubMed
PubMed Central
Google Scholar
Thornton DJ, Davies JR, Kraayenbrink M, Richardson PS, Sheehan JK, Carlstedt I. Mucus glycoproteins from 'normal' human tracheobronchial secretion. Biochem J. 1990;265:179–86.
Article
CAS
PubMed
PubMed Central
Google Scholar
Coles SJ, Reid L. Inhibition of glycoconjugate secretion by colchicine and cytochalasin B. An in vitro study of human airway. Cell Tissue Res. 1981;214:107–18.
Article
CAS
PubMed
Google Scholar
Carlstedt I, Sheehan JK. Macromolecular properties and polymeric structure of mucus glycoproteins. CIBA Found Symp. 1984;109:157–72.
CAS
PubMed
Google Scholar
Coles SJ, Bhaskar KR, O'Sullivan DD, Neill KH, Reid LM. Airway mucus: composition and regulation of its secretion by neuropeptides in vitro. CIBA Found Symp. 1984;109:40–60.
CAS
PubMed
Google Scholar
Boat TF, Kleinerman JI. Human respiratory tract secretions. 2. Effect of cholinergic and adrenergic agents on in vitro release of protein and mucous glycoprotein. Chest. 1975;67:32S–4S.
Article
CAS
PubMed
Google Scholar
Zachara NE, Gooley AA. Identification of glycosylation sites in mucin peptides by edman degradation. Methods Mol Biol. 2000;125:121–8.
CAS
PubMed
Google Scholar
Thornton DJ, Howard M, Khan N, Sheehan JK. Identification of two glycoforms of the MUC5B mucin in human respiratory mucus - evidence for a cysteine-rich sequence repeated within the molecule. J Biol Chem. 1997;272:9561–6.
Article
CAS
PubMed
Google Scholar
Xia BY, Royall JA, Damera G, Sachdev GP, Cummings RD. Altered O-glycosylation and sulfation of airway mucins associated with cystic fibrosis. Glycobiology. 2005;15:747–75.
Article
CAS
PubMed
Google Scholar
Jentoft N. Why are proteins O-glycosylated? Trends Biochem Sci. 1990;15:291–4.
Article
CAS
PubMed
Google Scholar
Sturgess J, Reid L. Secretory activity of the human bronchial mucous glands in vitro. Exp Mol Pathol. 1972;16:362–81.
Article
CAS
PubMed
Google Scholar
Rose MC, Brown CF, Jacoby JZ, Lynn WS, Kaufman B. Biochemical properties of tracheobronchial mucins from cystic fibrosis and non-cystic fibrosis individuals. Pediatr Res. 1987;22:545–51.
Article
CAS
PubMed
Google Scholar
Carlstedt I, Sheehan JK. Is the macromolecular architecture of cervical, respiratory and gastric mucins the same? Biochem Soc Trans. 1984;12:615–7.
Article
CAS
PubMed
Google Scholar
Lai SK, Wang Y-Y, Wirtz D, Hanes J. Micro- and macrorheology of mucus. Adv Drug Deliv Rev. 2009;61:86–100.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vasquez PA, Jin Y, Palmer E, Hill D, Forest MG. Modeling and simulation of mucus flow in human bronchial epithelial cell cultures – part I: idealized axisymmetric swirling flow. PLoS Comput Biol. 2016;12:e1004872.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cheang UK, Roy D, Lee JH, Kim MJ. Fabrication and magnetic control of bacteria-inspired robotic microswimmers. Appl Phys Lett. 2010;97.
Ali J, Cheang UK, Martindale JD, Jabbarzadeh M, Fu HC, Kim MJ. Bacteria-inspired nanorobots with flagellar polymorphic transformations and bundling. Sci Rep. 2017;7.