Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases (original) (raw)

References

• Adkins B, Leclerc C, Marshall-Clarke S (2004) Neonatal adaptive immunity comes of age. Nat Rev Immunol 4:553–564
  Article CAS PubMed Google Scholar
• Anagnostopoulou P, Dai L, Schatterny J, Hirtz S, Duerr J, Mall MA (2010) Allergic airway inflammation induces a pro-secretory epithelial ion transport phenotype in mice. Eur Respir J 36:1436–1447
  Article CAS PubMed Google Scholar
• Anagnostopoulou P, Riederer B, Duerr J, Michel S, Binia A, Agrawal R, Liu X, Kalitzki K, Xiao F, Chen M, Schatterny J, Hartmann D, Thum T, Kabesch M, Soleimani M, Seidler U, Mall MA (2012) SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation. J Clin Invest 122:3629–3634
  Article CAS PubMed PubMed Central Google Scholar
• Anderson WH, Coakley RD, Button B, Henderson AG, Zeman KL, Alexis NE, Peden DB, Lazarowski ER, Davis CW, Bailey S, Fuller F, Almond M, Qaqish B, Bordonali E, Rubinstein M, Bennett WD, Kesimer M, Boucher RC (2015) The relationship of mucus concentration (Hydration) to mucus osmotic pressure and transport in chronic bronchitis. Am J Respir Crit Care Med 192:182–190
  Article PubMed PubMed Central Google Scholar
• Bakouh N, Bienvenu T, Thomas A, Ehrenfeld J, Liote H, Roussel D, Duquesnoy P, Farman N, Viel M, Cherif-Zahar B, Amselem S, Taam RA, Edelman A, Planelles G, Sermet-Gaudelus I (2013) Characterization of SLC26A9 in patients with CF-like lung disease. Hum Mutat 34:1404–1414
  Article CAS PubMed Google Scholar
• Bateman JR, Pavia D, Sheahan NF, Agnew JE, Clarke SW (1983) Impaired tracheobronchial clearance in patients with mild stable asthma. Thorax 38:463–467
  Article CAS PubMed PubMed Central Google Scholar
• Baum GL, Zwas ST, Katz I, Roth Y (1990) Mucociliary clearance from central airways in patients with excessive sputum production with and without primary ciliary dyskinesia. Chest 98:608–612
  Article CAS PubMed Google Scholar
• Becq F, Mall MA, Sheppard DN, Conese M, Zegarra-Moran O (2011) Pharmacological therapy for cystic fibrosis: from bench to bedside. J Cyst Fibros 10(Suppl 2):S129–S145
  Article CAS PubMed Google Scholar
• Bertrand CA, Zhang R, Pilewski JM, Frizzell RA (2009) SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia. J Gen Physiol 133:421–438
  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, Watson JD, Smith AT, Schuster BS, Hanes J, Grizzle WE, Sorscher EJ, Tearney GJ, Rowe SM (2014) A functional anatomic defect of the cystic fibrosis airway. Am J Respir Crit Care Med 190:421–432
  Article PubMed PubMed Central Google Scholar
• Bonora M, Riffault L, Marie S, Mall M, Clement A, Tabary O (2011) Morphological analysis of the trachea and pattern of breathing in betaENaC-Tg mice. Respir Physiol Neurobiol 178:346–348
  Article CAS PubMed Google Scholar
• Bonser LR, Zlock L, Finkbeiner W, Erle DJ (2016) Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma. J Clin Invest 126:2367–2371
  Article PubMed PubMed Central Google Scholar
• Boucher RC (2007) Cystic fibrosis: a disease of vulnerability to airway surface dehydration. Trends Mol Med 13:231–240
  Article CAS PubMed Google Scholar
• Boucher RC, Stutts MJ, Knowles MR, Cantley L, Gatzy JT (1986) Na+ transport in cystic fibrosis respiratory epithelia. abnormal basal rate and response to adenylate cyclase activation. J Clin Invest 78:1245–1252
  Article CAS PubMed PubMed Central Google Scholar
• Button B, Cai LH, Ehre C, Kesimer M, Hill DB, Sheehan JK, Boucher RC, Rubinstein M (2012) A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science 337:937–941
  Article CAS PubMed PubMed Central Google Scholar
• Button B, Anderson WH, Boucher RC (2016) Mucus hyperconcentration as a unifying aspect of the chronic bronchitic phenotype. Ann Am Thorac Soc 13(Suppl 2):S156–S162
  PubMed Google Scholar
• Byers DE, Holtzman MJ (2011) Alternatively activated macrophages and airway disease. Chest 140:768–774
  Article CAS PubMed PubMed Central Google Scholar
• Byrne AJ, Mathie SA, Gregory LG, Lloyd CM (2015) Pulmonary macrophages: key players in the innate defence of the airways. Thorax 70:1189–1196
  Article PubMed Google Scholar
• Cantin AM, Hanrahan JW, Bilodeau G, Ellis L, Dupuis A, Liao J, Zielenski J, Durie P (2006) Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Am J Respir Crit Care Med 173:1139–1144
  Article CAS PubMed Google Scholar
• Cantin AM, Hartl D, Konstan MW, Chmiel JF (2015) Inflammation in cystic fibrosis lung disease: pathogenesis and therapy. J Cyst Fibros 14:419–430
  Article CAS PubMed Google Scholar
• Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL (2007) Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med 13:851–856
  Article CAS PubMed Google Scholar
• Chen Y, Garvin LM, Nickola TJ, Watson AM, Colberg-Poley AM, Rose MC (2014) IL-1beta induction of MUC5AC gene expression is mediated by CREB and NF-kappaB and repressed by dexamethasone. Am J Physiol Lung Cell Mol Physiol 306:L797–L807
  Article CAS PubMed PubMed Central Google Scholar
• Churg A, Wright JL (2005) Proteases and emphysema. Curr Opin Pulm Med 11:153–159
  Article PubMed Google Scholar
• Clunes LA, Davies CM, Coakley RD, Aleksandrov AA, Henderson AG, Zeman KL, Worthington EN, Gentzsch M, Kreda SM, Cholon D, Bennett WD, Riordan JR, Boucher RC, Tarran R (2012) Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J 26:533–545
  Article CAS PubMed PubMed Central Google Scholar
• Cobos-Correa A, Trojanek JB, Diemer S, Mall MA, Schultz C (2009) Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation. Nat Chem Biol 5:628–630
  Article CAS PubMed Google Scholar
• De Boeck K, Amaral MD (2016) Progress in therapies for cystic fibrosis. Lancet Respir Med 4:662–674
  Article PubMed CAS Google Scholar
• Dinarello CA, Simon A, van der Meer JW (2012) Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 11:633–652
  Article CAS PubMed PubMed Central Google Scholar
• Donaldson SH, Corcoran TE, Laube BL, Bennett WD (2007) Mucociliary clearance as an outcome measure for cystic fibrosis clinical research. Proc Am Thorac Soc 4:399–405
  Article PubMed Google Scholar
• Doring G, Bragonzi A, Paroni M, Akturk FF, Cigana C, Schmidt A, Gilpin D, Heyder S, Born T, Smaczny C, Kohlhaufl M, Wagner TO, Loebinger MR, Bilton D, Tunney MM, Elborn JS, Pier GB, Konstan MW, Ulrich M (2014) BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs. J Cyst Fibros 13:156–163
  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 (2013) Acquired CFTR dysfunction in the lower airways in COPD. Chest 144:498–506
• Evans CM, Kim K, Tuvim MJ, Dickey BF (2009) Mucus hypersecretion in asthma: causes and effects. Curr Opin Pulm Med 15:4–11
  Article CAS PubMed PubMed Central Google Scholar
• Evans CM, Raclawska DS, Ttofali F, Liptzin DR, Fletcher AA, Harper DN, McGing MA, McElwee MM, Williams OW, Sanchez E, Roy MG, Kindrachuk KN, Wynn TA, Eltzschig HK, Blackburn MR, Tuvim MJ, Janssen WJ, Schwartz DA, Dickey BF (2015) The polymeric mucin Muc5ac is required for allergic airway hyperreactivity. Nat Commun 6:6281
  Article CAS PubMed PubMed Central Google Scholar
• Fahy JV (2015) Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol 15:57–65
  Article CAS PubMed PubMed Central Google Scholar
• Fahy JV, Dickey BF (2010) Airway mucus function and dysfunction. N Engl J Med 363:2233–2247
  Article CAS PubMed PubMed Central Google Scholar
• Fellner RC, Terryah ST, Tarran R (2016) Inhaled protein/peptide-based therapies for respiratory disease. Mol Cell Pediatr 3:16
  Article PubMed PubMed Central Google Scholar
• Fritzsching B, Zhou-Suckow Z, Trojanek JB, Schubert SC, Schatterny J, Hirtz S, Agrawal R, Muley T, Kahn N, Sticht C, Gunkel N, Welte T, Randell SH, Langer F, Schnabel P, Herth FJ, Mall MA (2015) Hypoxic epithelial necrosis triggers neutrophilic inflammation via IL-1 receptor signaling in cystic fibrosis lung disease. Am J Respir Crit Care Med 191:902–913
  Article CAS PubMed PubMed Central Google Scholar
• Fritzsching B, Hagner M, Dai L, Christochowitz S, Agrawal R., Van Bodegom C, Schmidt S, Schatterny J, Hirtz S, Brown R, Goritzka M, Duerr J, Zhou-Suckow Z, Mall MA (2016) Impaired mucus clearance exacerbates allergen-induced type 2 airway inflammation in juvenile mice. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2016.09.045
• Fujisawa T, Chang MM, Velichko S, Thai P, Hung LY, Huang F, Phuong N, Chen Y, Wu R (2011) NF-kappaB mediates IL-1beta- and IL-17A-induced MUC5B expression in airway epithelial cells. Am J Respir Cell Mol Biol 45:246–252
  Article CAS PubMed Google Scholar
• Gaggar A, Hector A, Bratcher PE, Mall MA, Griese M, Hartl D (2011) The role of matrix metalloproteinases in cystic fibrosis lung disease. Eur Respir J 38:721–727
  Article CAS PubMed PubMed Central Google Scholar
• Galluzzo M, Ciraolo E, Lucattelli M, Hoxha E, Ulrich M, Campa CC, Lungarella G, Doring G, Zhou-Suckow Z, Mall M, Hirsch E, De RV (2015) Genetic deletion and pharmacological inhibition of PI3K gamma reduces neutrophilic airway inflammation and lung damage in mice with cystic fibrosis-like lung disease. Mediators Inflamm 2015:545417
  Article PubMed PubMed Central CAS Google Scholar
• Gehrig S, Mall MA, Schultz C (2012) Spatially resolved monitoring of neutrophil elastase activity with ratiometric fluorescent reporters. Angew Chem Int Ed Engl 51:6258–6261
  Article CAS PubMed Google Scholar
• Gehrig S, Duerr J, Weitnauer M, Wagner CJ, Graeber SY, Schatterny J, Hirtz S, Belaaouaj A, Dalpke AH, Schultz C, Mall MA (2014) Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosis-like lung disease. Am J Respir Crit Care Med 189:1082–1092
  Article PubMed Google Scholar
• Geiser M, Quaile O, Wenk A, Wigge C, Eigeldinger-Berthou S, Hirn S, Schaffler M, Schleh C, Moller W, Mall MA, Kreyling WG (2013) Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease. Part Fibre Toxicol 10:19
  Article CAS PubMed PubMed Central Google Scholar
• Geiser M, Wigge C, Conrad ML, Eigeldinger-Berthou S, Kunzi L, Garn H, Renz H, Mall MA (2014) Nanoparticle uptake by airway phagocytes after fungal spore challenge in murine allergic asthma and chronic bronchitis. BMC Pulm Med 14:116
  Article PubMed PubMed Central CAS Google Scholar
• Ghosh A, Boucher RC, Tarran R (2015) Airway hydration and COPD. Cell Mol Life Sci 72:3637–3652
  Article CAS PubMed PubMed Central Google Scholar
• Gibson RL, Burns JL, Ramsey BW (2003) Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 168:918–951
  Article PubMed Google Scholar
• Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593–604
  Article CAS PubMed Google Scholar
• Graeber SY, Zhou-Suckow Z, Schatterny J, Hirtz S, Boucher RC, Mall MA (2013) Hypertonic saline is effective in the prevention and treatment of mucus obstruction, but not airway inflammation, in mice with chronic obstructive lung disease. Am J Respir Cell Mol Biol 49:410–417
  Article CAS PubMed PubMed Central Google Scholar
• Gustafsson JK, Ermund A, Ambort D, Johansson ME, Nilsson HE, Thorell K, Hebert H, Sjovall H, Hansson GC (2012) Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J Exp Med 209:1263–1272
  Article CAS PubMed PubMed Central Google Scholar
• Hammad H, Lambrecht BN (2015) Barrier epithelial cells and the control of Type 2 immunity. Immunity 43:29–40
  Article CAS PubMed Google Scholar
• Hartl D, Gaggar A, Bruscia E, Hector A, Marcos V, Jung A, Greene C, McElvaney G, Mall M, Doring G (2012) Innate immunity in cystic fibrosis lung disease. J Cyst Fibros 11:363–382
  Article CAS PubMed Google Scholar
• Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277:2002–2004
  Article CAS PubMed Google Scholar
• Hays SR, Fahy JV (2003) The role of mucus in fatal asthma. Am J Med 115:68–69
  Article PubMed Google Scholar
• Hector A, Kormann MS, Mack I, Latzin P, Casaulta C, Kieninger E, Zhou Z, Yildirim AO, Bohla A, Rieber N, Kappler M, Koller B, Eber E, Eickmeier O, Zielen S, Eickelberg O, Griese M, Mall MA, Hartl D (2011) The Chitinase-like protein YKL-40 modulates cystic fibrosis lung disease. PLoS ONE 6:e24399
  Article CAS PubMed PubMed Central Google Scholar
• Henderson AG, Ehre C, Button B, Abdullah LH, Cai LH, Leigh MW, DeMaria GC, Matsui H, Donaldson SH, Davis CW, Sheehan JK, Boucher RC, Kesimer M (2014) Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure. J Clin Invest 124:3047–3060
  Article CAS PubMed PubMed Central Google Scholar
• Hiemstra PS, McCray PB Jr, Bals R (2015) The innate immune function of airway epithelial cells in inflammatory lung disease. Eur Respir J 45:1150–1162
  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, Stoltz DA, Welsh MJ (2014) Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science 345:818–822
  Article CAS PubMed PubMed Central Google Scholar
• Hogg JC (2004) Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364:709–721
  Article PubMed Google Scholar
• Hogg JC, Timens W (2009) The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol 4:435–459
  Article CAS PubMed Google Scholar
• Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350:2645–2653
  Article CAS PubMed Google Scholar
• Houtmeyers E, Gosselink R, Gayan-Ramirez G, Decramer M (1999) Effects of drugs on mucus clearance. Eur Respir J 14:452–467
  Article CAS PubMed Google Scholar
• Hu HY, Gehrig S, Reither G, Subramanian D, Mall MA, Plettenburg O, Schultz C (2014) FRET-based and other fluorescent proteinase probes. Biotechnol J 9:266–281
  Article CAS PubMed Google Scholar
• Jaecklin T, Duerr J, Huang H, Rafii M, Bear CE, Ratjen F, Pencharz P, Kavanagh BP, Mall MA, Grasemann H (2014) Lung arginase expression and activity is increased in cystic fibrosis mouse models. J Appl Physiol 117(1985):284–288
  Article PubMed Google Scholar
• Janssen WJ, Stefanski AL, Bochner BS, Evans CM (2016) Control of lung defence by mucins and macrophages: ancient defence mechanisms with modern functions. Eur Respir J 48:1201–1214
  Article PubMed Google Scholar
• Jia J, Conlon TM, Ballester LC, Seimetz M, Bednorz M, Zhou-Suckow Z, Weissmann N, Eickelberg O, Mall MA, Yildirim AO (2016) Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice. Am J Physiol Lung Cell Mol Physiol 311:L602–L610
  Article PubMed Google Scholar
• Johannesson B, Hirtz S, Schatterny J, Schultz C, Mall MA (2012) CFTR regulates early pathogenesis of chronic obstructive lung disease in bENaC-overexpressing mice. PLoS ONE 7:e44059
  Article CAS PubMed PubMed Central Google Scholar
• Knowles MR, Boucher RC (2002) Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 109:571–577
  Article CAS PubMed PubMed Central Google Scholar
• Kopp BT, Sarzynski L, Khalfoun S, Hayes D Jr, Thompson R, Nicholson L, Long F, Castile R, Groner J (2015) Detrimental effects of secondhand smoke exposure on infants with cystic fibrosis. Pediatr Pulmonol 50:25–34
  Article PubMed Google Scholar
• Kuyper LM, Pare PD, Hogg JC, Lambert RK, Ionescu D, Woods R, Bai TR (2003) Characterization of airway plugging in fatal asthma. Am J Med 115:6–11
  Article PubMed Google Scholar
• Landgraf-Rauf K, Anselm B, Schaub B (2016) The puzzle of immune phenotypes of childhood asthma. Mol Cell Pediatr 3:27
  Article PubMed PubMed Central Google Scholar
• Lewis CC, Aronow B, Hutton J, Santeliz J, Dienger K, Herman N, Finkelman FD, Wills-Karp M (2009) Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung. J Allergy Clin Immunol 123:795–804
  Article CAS PubMed PubMed Central Google Scholar
• Livraghi A, Grubb BR, Hudson EJ, Wilkinson KJ, Sheehan JK, Mall MA, O’Neal WK, Boucher RC, Randell SH (2009) Airway and lung pathology due to mucosal surface dehydration in b-epithelial Na + channel-overexpressing mice: role of TNF-a and IL-4Ra signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment. J Immunol 182:4357–4367
  Article CAS PubMed PubMed Central Google Scholar
• Livraghi-Butrico A, Kelly EJ, Klem ER, Dang H, Wolfgang MC, Boucher RC, Randell SH, O’Neal WK (2012) Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation. Mucosal Immunol 5:397–408
  Article CAS PubMed PubMed Central Google Scholar
• Livraghi-Butrico A, Grubb BR, Wilkinson KJ, Volmer AS, Burns KA, Evans CM, O’Neal WK, Boucher RC (2016) Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol (in press)
• Lloyd CM, Saglani S (2015) Epithelial cytokines and pulmonary allergic inflammation. Curr Opin Immunol 34:52–58. doi:10.1016/j.coi.2015.02.001
  Article CAS PubMed Google Scholar
• Locke LW, Myerburg MM, Weiner DJ, Markovetz MR, Parker RS, Muthukrishnan A, Weber L, Czachowski MR, Lacy RT, Pilewski JM, Corcoran TE (2016) Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung. Eur Respir J 47:1392–1401
  Article PubMed Google Scholar
• Lohi H, Kujala M, Makela S, Lehtonen E, Kestila M, Saarialho-Kere U, Markovich D, Kere J (2002) Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9. J Biol Chem 277:14246–14254
  Article CAS PubMed Google Scholar
• Lukens JR, Gross JM, Kanneganti TD (2012) IL-1 family cytokines trigger sterile inflammatory disease. Front Immunol 3:315
  Article PubMed PubMed Central Google Scholar
• Mack I, Hector A, Ballbach M, Kohlhaufl J, Fuchs KJ, Weber A, Mall MA, Hartl D (2015) The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases. Mol Cell Pediatr 2:3–0014
  Article PubMed PubMed Central Google Scholar
• Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. an overview of cell death. Am J Pathol 146:3–15
  CAS PubMed PubMed Central Google Scholar
• Mall MA (2008) Role of cilia, mucus, and airway surface liquid in mucociliary dysfunction: lessons from mouse models. J Aerosol Med Pulm Drug Deliv 21:13–24
  Article CAS PubMed Google Scholar
• Mall MA (2009) Role of the amiloride-sensitive epithelial Na + channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease. Exp Physiol 94:171–174
  Article CAS PubMed Google Scholar
• Mall MA (2016) Unplugging mucus in cystic fibrosis and chronic obstructive pulmonary disease. Ann Am Thorac Soc 13(Suppl 2):S177–S185. doi:10.1513/AnnalsATS.201509-641KV.:S177-S185
  PubMed Google Scholar
• Mall MA, Galietta LJ (2015) Targeting ion channels in cystic fibrosis. J Cyst Fibros 14:561–570
  Article CAS PubMed Google Scholar
• Mall MA, Hartl D (2014) CFTR: cystic fibrosis and beyond. Eur Respir J 44:1042–1054
  Article CAS PubMed Google Scholar
• Mall M, Bleich M, Greger R, Schreiber R, Kunzelmann K (1998) The amiloride inhibitable Na+ conductance is reduced by CFTR in normal but not in cystic fibrosis airways. J Clin Invest 102:15–21
  Article CAS PubMed PubMed Central Google Scholar
• Mall M, Grubb BR, Harkema JR, O’Neal WK, Boucher RC (2004) Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 10:487–493
  Article CAS PubMed Google Scholar
• Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O’Neal WK, Boucher RC (2008) Development of chronic bronchitis and emphysema in b-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med 177:730–742
  Article CAS PubMed Google Scholar
• Mall MA, Button B, Johannesson B, Zhou Z, Livraghi A, Caldwell RA, Schubert SC, Schultz C, O’Neal WK, Pradervand S, Hummler E, Rossier BC, Grubb BR, Boucher RC (2010) Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with betaENaC-overexpressing mice. J Biol Chem 285:26945–26955
  Article CAS PubMed PubMed Central Google Scholar
• Mall MA, Graeber SY, Stahl M, Zhou-Suckow Z (2014) Early cystic fibrosis lung disease: role of airway surface dehydration and lessons from preventive rehydration therapies in mice. Int J Biochem Cell Biol 52:174–179
• Mall MA, Stahl M, Graeber SY, Sommerburg O, Kauczor HU, Wielputz MO (2016) Early detection and sensitive monitoring of CF lung disease: prospects of improved and safer imaging. Pediatr Pulmonol 51:S49–S60
  Article PubMed Google Scholar
• Marcos V, Zhou-Suckow Z, Onder YA, Bohla A, Hector A, Vitkov L, Krautgartner WD, Stoiber W, Griese M, Eickelberg O, Mall MA, Hartl D (2015) Free DNA in cystic fibrosis airway fluids correlates with airflow obstruction. Mediators Inflamm 2015:408935
  Article PubMed PubMed Central CAS Google Scholar
• McCarthy C, Reeves EP, McElvaney NG (2016) The role of neutrophils in Alpha-1 antitrypsin deficiency. Ann Am Thorac Soc 13(Suppl 4):S297–S304
  Article PubMed Google Scholar
• Pavia D, Bateman JR, Sheahan NF, Agnew JE, Clarke SW (1985) Tracheobronchial mucociliary clearance in asthma: impairment during remission. Thorax 40:171–175
  Article CAS PubMed PubMed Central Google Scholar
• Quinton PM (2008) Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet 372:415–417
  Article CAS PubMed Google Scholar
• Raclawska DS, Ttofali F, Fletcher AA, Harper DN, Bochner BS, Janssen WJ, Evans CM (2016) Mucins and their sugars. critical mediators of hyperreactivity and inflammation. Ann Am Thorac Soc 13(Suppl 1):S98–S99
  PubMed Google Scholar
• Regnis JA, Robinson M, Bailey DL, Cook P, Hooper P, Chan HK, Gonda I, Bautovich G, Bye PT (1994) Mucociliary clearance in patients with cystic fibrosis and in normal subjects. Am J Respir Crit Care Med 150:66–71
  Article CAS PubMed Google Scholar
• Rose MC, Voynow JA (2006) Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 86:245–278
  Article CAS PubMed Google Scholar
• Rowan SA, Bradley JM, Bradbury I, Lawson J, Lynch T, Gustafsson P, Horsley A, O’Neill K, Ennis M, Elborn JS (2014) Lung clearance index is a repeatable and sensitive indicator of radiological changes in bronchiectasis. Am J Respir Crit Care Med 189:586–592
  Article PubMed Google Scholar
• Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O’Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM (2014) Muc5b is required for airway defence. Nature 505:412–416
  Article CAS PubMed Google Scholar
• Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET (2012) Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med 186:857–865
  Article CAS PubMed PubMed Central Google Scholar
• Saglani S, Mathie SA, Gregory LG, Bell MJ, Bush A, Lloyd CM (2009) Pathophysiological features of asthma develop in parallel in house dust mite-exposed neonatal mice. Am J Respir Cell Mol Biol 41:281–289
  Article CAS PubMed PubMed Central Google Scholar
• Saini Y, Dang H, Livraghi-Butrico A, Kelly EJ, Jones LC, O’Neal WK, Boucher RC (2014) Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration. BMC Genomics 15:726
  Article PubMed PubMed Central CAS Google Scholar
• Saini Y, Wilkinson KJ, Terrell KA, Burns KA, Livraghi-Butrico A, Doerschuk CM, O’Neal WK, Boucher RC (2015) Neonatal pulmonary macrophage depletion coupled to defective mucus clearance increases susceptibility to pneumonia and alters pulmonary immune responses. Am J Respir Cell Mol Biol 54:210–221
• Salomon JJ, Spahn S, Wang X, Fullekrug J, Bertrand CA, Mall MA (2016) Generation and functional characterization of epithelial cells with stable expression of SLC26A9 Cl- channels. Am J Physiol Lung Cell Mol Physiol 310:L593–L602
  Article PubMed Google Scholar
• Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490
  Article CAS PubMed Google Scholar
• Seys LJ, Verhamme FM, Dupont LL, Desauter E, Duerr J, Seyhan AA, Conickx G, Joos GF, Brusselle GG, Mall MA, Bracke KR (2015) Airway surface dehydration aggravates cigarette smoke-induced hallmarks of COPD in mice. PLoS ONE 10:e0129897
  Article PubMed PubMed Central CAS Google Scholar
• Shipley JM, Wesselschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD (1996) Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci U S A 93:3942–3946
  Article CAS PubMed PubMed Central Google Scholar
• Sly PD, Brennan S, Gangell C, de Klerk N, Murray C, Mott L, Stick SM, Robinson PJ, Robertson CF, Ranganathan SC (2009) Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 180:146–152
  Article PubMed Google Scholar
• Sly PD, Gangell CL, Chen L, Ware RS, Ranganathan S, Mott LS, Murray CP, Stick SM (2013) Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 368:1963–1970
  Article CAS PubMed Google Scholar
• Smaldone GC, Foster WM, O’Riordan TG, Messina MS, Perry RJ, Langenback EG (1993) Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease. Chest 103:1390–1396
  Article CAS PubMed Google Scholar
• Snodgrass AM, Tan PT, Soh SE, Goh A, Shek LP, van Bever HP, Gluckman PD, Godfrey KM, Chong YS, Saw SM, Kwek K, Teoh OH (2015) Tobacco smoke exposure and respiratory morbidity in young children. Tob Control 25(e2):e75–e82
• Solomon GM, Marshall SG, Ramsey BW, Rowe SM (2015) Breakthrough therapies: Cystic fibrosis (CF) potentiators and correctors. Pediatr Pulmonol 50(Suppl 40):S3–S13
  Article PubMed PubMed Central Google Scholar
• Solomon GM, Raju SV, Dransfield MT, Rowe SM (2016) Therapeutic approaches to acquired cystic fibrosis transmembrane conductance regulator dysfunction in chronic bronchitis. Ann Am Thorac Soc 13(Suppl 2):S169–S176
  PubMed Google Scholar
• Stahl M, Wielputz MO, Graeber SY, Joachim C, Sommerburg O, Kauczor HU, Puderbach M, Eichinger M, Mall MA (2016) Comparison of lung clearance index and magnetic resonance imaging for assessment of lung disease in children with cystic fibrosis. Am J Respir Crit Care Med doi:10.1164/rccm.201604-0893OC
• Stahr CS, Samarage CR, Donnelley M, Farrow N, Morgan KS, Zosky G, Boucher RC, Siu KK, Mall MA, Parsons DW, Dubsky S, Fouras A (2016) Quantification of heterogeneity in lung disease with image-based pulmonary function testing. Sci Rep 6:29438
  Article CAS PubMed PubMed Central Google Scholar
• Stanojevic S, Ratjen F (2016) Physiologic endpoints for clinical studies for cystic fibrosis. J Cyst Fibros 15:416–423
  Article PubMed Google Scholar
• Strug LJ, Gonska T, He G, Keenan K, Ip W, Boelle PY, Lin F, Panjwani N, Gong J, Li W, Soave D, Xiao B, Tullis E, Rabin H, Parkins MD, Price A, Zuberbuhler PC, Corvol H, Ratjen F, Sun L, Bear CE, Rommens JM (2016) Cystic fibrosis gene modifier SLC26A9 modulates airway response to CFTR-directed therapeutics. Hum Mol Genet (in press)
• Sun L, Rommens JM, Corvol H, Li W, Li X, Chiang TA, Lin F, Dorfman R, Busson PF, Parekh RV, Zelenika D, Blackman SM, Corey M, Doshi VK, Henderson L, Naughton KM, O’Neal WK, Pace RG, Stonebraker JR, Wood SD, Wright FA, Zielenski J, Clement A, Drumm ML, Boelle PY, Cutting GR, Knowles MR, Durie PR, Strug LJ (2012) Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat Genet 44:562–569
  Article CAS PubMed PubMed Central Google Scholar
• Trojanek JB, Cobos-Correa A, Diemer S, Kormann M, Schubert SC, Zhou-Suckow Z, Agrawal R, Duerr J, Wagner CJ, Schatterny J, Hirtz S, Sommerburg O, Hartl D, Schultz C, Mall MA (2014) Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema. Am J Respir Cell Mol Biol 51:709–720
  Article PubMed CAS Google Scholar
• Twigg MS, Brockbank S, Lowry P, FitzGerald SP, Taggart C, Weldon S (2015) The role of serine proteases and antiproteases in the cystic fibrosis lung. Mediators Inflamm 2015:293053. doi:10.1155/2015/293053
  Article PubMed PubMed Central CAS Google Scholar
• Vastag E, Matthys H, Zsamboki G, Kohler D, Daikeler G (1986) Mucociliary clearance in smokers. Eur J Respir Dis 68:107–113
  CAS PubMed Google Scholar
• Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R (2013) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 187:347–365
  Article CAS PubMed Google Scholar
• Wagner CJ, Schultz C, Mall MA (2016) Neutrophil elastase and matrix metalloproteinase 12 in cystic fibrosis lung disease. Mol Cell Pediatr 3:25
  Article PubMed PubMed Central Google Scholar
• Wanner A, Salathe M, O’Riordan TG (1996) Mucociliary clearance in the airways. Am J Respir Crit Care Med 154:1868–1902
  Article CAS PubMed Google Scholar
• Wielpütz MO, Mall MA (2015) Imaging modalities in cystic fibrosis: emerging role of MRI. Curr Opin Pulm Med 21:609–616
  Article PubMed Google Scholar
• Wielpütz MO, Eichinger M, Zhou Z, Leotta K, Hirtz S, Bartling SH, Semmler W, Kauczor HU, Puderbach M, Mall MA (2011) In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography. Eur Respir J 38:1060–1070
  Article PubMed Google Scholar
• Wielputz MO, Puderbach M, Kopp-Schneider A, Stahl M, Fritzsching E, Sommerburg O, Ley S, Sumkauskaite M, Biederer J, Kauczor HU, Eichinger M, Mall MA (2014) Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 189:956–965
  Article PubMed Google Scholar
• Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD (1998) Interleukin-13: central mediator of allergic asthma. Science 282:2258–2261
  Article CAS PubMed Google Scholar
• Yuan S, Hollinger M, Lachowicz-Scroggins ME, Kerr SC, Dunican EM, Daniel BM, Ghosh S, Erzurum SC, Willard B, Hazen SL, Huang X, Carrington SD, Oscarson S, Fahy JV (2015) Oxidation increases mucin polymer cross-links to stiffen airway mucus gels. Sci Transl Med 7:276ra27
  Article CAS PubMed PubMed Central Google Scholar
• Zegarra-Moran O, Galietta LJ (2016) CFTR pharmacology. Cell Mol Life Sci (in press)
• Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, Chapman HA Jr, Shapiro SD, Elias JA (2000) Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest 106:1081–1093
  Article CAS PubMed PubMed Central Google Scholar
• Zhou Z, Treis D, Schubert SC, Harm M, Schatterny J, Hirtz S, Duerr J, Boucher RC, Mall MA (2008) Preventive but not late amiloride therapy reduces morbidity and mortality of lung disease in bENaC-overexpressing mice. Am J Respir Crit Care Med 178:1245–1256
  Article CAS PubMed Google Scholar
• Zhou Z, Duerr J, Johannesson B, Schubert SC, Treis D, Harm M, Graeber SY, Dalpke A, Schultz C, Mall MA (2011) The bENaC-overexpressing mouse as a model of cystic fibrosis lung disease. J Cyst Fibros 10(Suppl 2):S172–S182
  Article CAS PubMed Google Scholar
• Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, Zhang Y, Elias JA (1999) Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 103:779–788
  Article CAS PubMed PubMed Central Google Scholar
• Zuelzer WW, Newton WA (1949) The pathogenesis of fibrocystic disease of the pancreas; a study of 36 cases with special reference to the pulmonary lesions. Pediatrics 4:53–69
  CAS PubMed Google Scholar

Download references