Novel drug targets for asthma and COPD: Lessons learned from invitro and invivo models

Pulmonary Pharmacology and Therapeutics

Volumn 29, Issue 2, 2014, Pages 181-198

  Baker, Katie E ^a   Bonvini, Sara J ^a   Donovan, Chantal ^b   Foong, Rachel E ^c   Han, Bing ^d,e   Jha, Aruni ^f   Shaifta, Yasin ^g   Smit, Marieke ^d,e   Johnson, Jill R ^a   Moir, Lyn M ^h,i  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^d UNIVERSITY OF GRONINGEN   (Netherlands)

^e UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^f UNIVERSITY OF MANITOBA   (Canada)

^g KING'S COLLEGE LONDON   (United Kingdom)

^h WOOLCOCK INSTITUTE OF MEDICAL RESEARCH   (Australia)

ⁱ UNIVERSITY OF SYDNEY   (Australia)

Author keywords

G protein coupled receptor; Inflammation; Kinase; Therapeutic targets; Transient receptor potential channel; Vitamin D

Indexed keywords

BATEFENTEROL; CHOLINERGIC RECEPTOR BLOCKING AGENT; CORTICOSTEROID; CYCLIC AMP DEPENDENT PROTEIN KINASE ANCHORING PROTEIN; DUPILUMAB; FIBOFLAPON; FLUTICASONE FUROATE PLUS VILANTEROL; FLUTICASONE PROPIONATE PLUS SALMETEROL; G PROTEIN COUPLED RECEPTOR; GLYCOPYRRONIUM BROMIDE PLUS INDACATEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 1BETA ANTIBODY; INTERLEUKIN 8 ANTIBODY; MACROLIDE; MATRIX METALLOPROTEINASE; MEPOLIZUMAB; MONTELUKAST; OLODATEROL; OLODATEROL PLUS TIOTROPIUM BROMIDE; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; PHOSPHOTRANSFERASE; PHOSPHOTRANSFERASE INHIBITOR; PROTEINASE INHIBITOR; RECOMBINANT INTERLEUKIN 1ALPHA; TIOTROPIUM BROMIDE; TRANSIENT RECEPTOR POTENTIAL CHANNEL; VITAMIN D; ANTIASTHMATIC AGENT; ANTIINFLAMMATORY AGENT; PROTEIN KINASE INHIBITOR;

ADD ON THERAPY; ALLERGIC ASTHMA; ANEMIA; ARTICLE; ASTHMA; CHOLINERGIC STIMULATION; CHRONIC OBSTRUCTIVE LUNG DISEASE; CORTICOSTEROID THERAPY; DRUG TARGETING; HEMATOLOGIC DISEASE; HUMAN; HYPERTENSION; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; ANIMAL; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

ANIMALS; ANTI-ASTHMATIC AGENTS; ANTI-INFLAMMATORY AGENTS; ASTHMA; HUMANS; PHOSPHODIESTERASE INHIBITORS; PROTEASE INHIBITORS; PROTEIN KINASE INHIBITORS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; TRANSIENT RECEPTOR POTENTIAL CHANNELS; VITAMIN D;

EID: 84922659414     PISSN: 10945539     EISSN: 15229629     Source Type: Journal    
DOI: 10.1016/j.pupt.2014.05.008     Document Type: Article

References (305)

1. WHO Asthma 2013, World Health Organization. http://www.who.int/mediacentre/factsheets/fs307/en/.
2. Mannino D.M., Buist A.S. Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007, 370:765-773.
3. Miles M.C., Donohue J.F., Ohar J.A. Optimum bronchodilator combinations in chronic obstructive pulmonary disease: what is the current evidence?. Drugs 2012, 72:301-308.
4. Lotvall J., Akdis C.A., Bacharier L.B., Bjermer L., Casale T.B., Custovic A., et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011, 127:355-360.
5. Chu E.K., Drazen J.M. Asthma: one hundred years of treatment and onward. Am J Respir Crit Care Med 2005, 171:1202-1208.
6. Ilmarinen P., Kankaanranta H. Eosinophil apoptosis as a therapeutic target in allergic asthma. Basic Clin Pharmacol Toxicol 2014, 114:109-117.
7. Nissim Ben Efraim A.H., Levi-Schaffer F. Tissue remodeling and angiogenesis in asthma: the role of the eosinophil. Ther Adv Respir Dis 2008, 2:163-171.
8. Garcia G., Taille C., Laveneziana P., Bourdin A., Chanez P., Humbert M. Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev Off J Eur Respir Soc 2013, 22:251-257.
9. O'Byrne P.M. The demise of anti IL-5 for asthma, or not. Am J Respir Crit Care Med 2007, 176:1059-1060.
10. Kips J.C., O'Connor B.J., Langley S.J., Woodcock A., Kerstjens H.A., Postma D.S., et al. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 2003, 167:1655-1659.
11. Nair P., Pizzichini M.M., Kjarsgaard M., Inman M.D., Efthimiadis A., Pizzichini E., et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N. Engl J Med 2009, 360:985-993.
12. Pavord I.D., Korn S., Howarth P., Bleecker E.R., Buhl R., Keene O.N., et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012, 380:651-659.
13. Walsh G.M. An update on biologic-based therapy in asthma. Immunotherapy 2013, 5:1255-1264.
14. Wenzel S., Ford L., Pearlman D., Spector S., Sher L., Skobieranda F., et al. Dupilumab in persistent asthma with elevated eosinophil levels. N. Engl J Med 2013, 368:2455-2466.
15. Corren J., Lemanske R.F., Hanania N.A., Korenblat P.E., Parsey M.V., Arron J.R., et al. Lebrikizumab treatment in adults with asthma. N. Engl J Med 2011, 365:1088-1098.
16. Jia G., Erickson R.W., Choy D.F., Mosesova S., Wu L.C., Solberg O.D., et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J allergy Clin Immunol 2012, 130:647-654.
17. Noonan M., Korenblat P., Mosesova S., Scheerens H., Arron J.R., Zheng Y., et al. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J allergy Clin Immunol 2013, 132:567-574. e12.
18. Zeki A.A., Thai P., Kenyon N.J., Wu R. Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells. Respir Res 2012, 13:38.
19. Wang W., Le W., Ahuja R., Cho D.Y., Hwang P.H., Upadhyay D. Inhibition of inflammatory mediators: role of statins in airway inflammation. Otolaryngol-Head Neck Surg - Off J Am Acad Otolaryngol-Head Neck Surg 2011, 144:982-987.
20. Huang C.F., Peng H.J., Wu C.C., Lo W.T., Shih Y.L., Wu T.C. Effect of oral administration with pravastatin and atorvastatin on airway hyperresponsiveness and allergic reactions in asthmatic mice. Ann allergy, asthma & Immunol - Off Publ Am Coll Allergy Asthma Immunol 2013, 110:11-17.
21. Walker D.Y., Edwards K.L. Statins in the treatment of asthma. Am J Health-Sys Pharm - AJHP - Off J Am Soc Health-Sys Pharm 2013, 70:1661-1669.
22. Zeki A.A., Oldham J., Wilson M., Fortenko O., Goyal V., Last M., et al. Statin use and asthma control in patients with severe asthma. BMJ Open 2013, 3.
23. Tse S.M., Li L., Butler M.G., Fung V., Kharbanda E.O., Larkin E.K., et al. Statin exposure is associated with decreased asthma-related emergency department visits and oral corticosteroid use. Am J Respir Crit care Med 2013, 188:1076-1082.
24. Maneechotesuwan K., Kasetsinsombat K., Wamanuttajinda V., Wongkajornsilp A., Barnes P.J. Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells. Clin Exp allergy - J Br Soc Allergy Clin Immunol 2013, 43:212-222.
25. Beigelman A., Gunsten S., Mikols C.L., Vidavsky I., Cannon C.L., Brody S.L., et al. Azithromycin attenuates airway inflammation in a noninfectious mouse model of allergic asthma. Chest 2009, 136:498-506.
26. Reiter J., Demirel N., Mendy A., Gasana J., Vieira E.R., Colin A.A., et al. Macrolides for the long-term management of asthma-a meta-analysis of randomized clinical trials. Allergy 2013, 68:1040-1049.
27. Brusselle G.G., Vanderstichele C., Jordens P., Deman R., Slabbynck H., Ringoet V., et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 2013, 68:322-329.
28. Bathoorn E., Kerstjens H., Postma D., Timens W., MacNee W. Airways inflammation and treatment during acute exacerbations of COPD. Int J Chronic Obstr Pulm Dis 2008, 3:217-229.
29. Botelho F.M., Bauer C.M., Finch D., Nikota J.K., Zavitz C.C., Kelly A., et al. IL-1alpha/IL-1R1 expression in chronic obstructive pulmonary disease and mechanistic relevance to smoke-induced neutrophilia in mice. PloS one 2011, 6:e28457.
30. Keatings V.M., Collins P.D., Scott D.M., Barnes P.J. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit care Med 1996, 153:530-534.
31. Schild K., Knobloch J., Yakin Y., Jungck D., Urban K., Muller K., et al. IL-5 release of CD4+ non-effector lymphocytes is increased in COPD-modulating effects of moxifloxacin and dexamethasone. Int Immunopharmacol 2011, 11:444-448.
32. Molfino N.A., Gossage D., Kolbeck R., Parker J.M., Geba G.P. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy - J Br Soc Allergy Clin Immunol 2012, 42:712-737.
33. Agusti A., Edwards L.D., Rennard S.I., MacNee W., Tal-Singer R., Miller B.E., et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PloS one 2012, 7. e37483.
34. Celli B.R., Locantore N., Yates J., Tal-Singer R., Miller B.E., Bakke P., et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit care Med 2012, 185:1065-1072.
35. Zhang J., Chu S., Zhong X., Lao Q., He Z., Liang Y. Increased expression of CD4+IL-17+ cells in the lung tissue of patients with stable chronic obstructive pulmonary disease (COPD) and smokers. Int Immunopharmacol 2013, 15:58-66.
36. Kawayama T., Okamoto M., Imaoka H., Kato S., Young H.A., Hoshino T. Interleukin-18 in pulmonary inflammatory diseases. J interferon Cytokine Res - Off J Int Soc Interferon Cytokine Res 2012, 32:443-449.
37. Saha S., Doe C., Mistry V., Siddiqui S., Parker D., Sleeman M., et al. Granulocyte-macrophage colony-stimulating factor expression in induced sputum and bronchial mucosa in asthma and COPD. Thorax 2009, 64:671-676.
38. Ito K., Ito M., Elliott W.M., Cosio B., Caramori G., Kon O.M., et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N. Engl J Med 2005, 352:1967-1976.
39. Anagnostis A., Neofytou E., Soulitzis N., Kampas D., Drositis I., Dermitzaki D., et al. Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction. Eur J Clin Invest 2013, 43:1299-1306.
40. Stampfli M.R., Anderson G.P. How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat Rev Immunol 2009, 9:377-384.
41. Vlahos R., Bozinovski S. Recent advances in pre-clinical mouse models of COPD. Clin Sci 2014, 126:253-265.
42. Yang X.D., Corvalan J.R., Wang P., Roy C.M., Davis C.G. Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states. J Leukoc Biology 1999, 66:401-410.
43. Mahler D.A., Huang S., Tabrizi M., Bell G.M. Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study. Chest 2004, 126:926-934.
44. Meurs H., Dekkers B.G., Maarsingh H., Halayko A.J., Zaagsma J., Gosens R. Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target. Pulm Pharmacol Ther 2013, 26:145-155.
45. Schmidt M., Dekker F.J., Maarsingh H. Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol Rev 2013, 65:670-709.
46. Nelson H.S. Beta-adrenergic bronchodilators. N. Engl J Med 1995, 333:499-506.
47. Dekkers B.G., Racke K., Schmidt M. Distinct PKA and Epac compartmentalization in airway function and plasticity. Pharmacol Ther 2013, 137:248-265.
48. Cazzola M., Matera M.G. Emerging inhaled bronchodilators: an update. Eur Respir J - Off J Eur Soc Clin Respir Physiol 2009, 34:757-769.
49. Tamura G., Ohta K. Adherence to treatment by patients with asthma or COPD: comparison between inhaled drugs and transdermal patch. Respir Med 2007, 101:1895-1902.
50. Cazzola M., Calzetta L., Matera M.G. β(2) -adrenoceptor agonists: current and future direction. Br J Pharmacol 2011, 163:4-17.
51. Bouyssou T., Casarosa P., Naline E., Pestel S., Konetzki I., Devillier P., et al. Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models. J Pharmacol Exp Ther 2010, 334:53-62.
52. Gibb A., Yang L.P. Olodaterol: first global approval. Drugs 2013, 73:1841-1846.
53. Clinicaltrials.gov . http://clinicaltrials.gov/ct2/results%3Fterm%3Dolodaterol+asthma.
54. Smit M., Zuidhof A.B., Bos S.I., Maarsingh H., Gosens R., Zaagsma J., et al. Bronchoprotection by olodaterol is synergistically enhanced by tiotropium in a guinea pig model of allergic asthma. J Pharmacol Exp Ther 2014, 348:303-310.
55. Yohannes A.M., Connolly M.J., Hanania N.A. Ten years of tiotropium: clinical impact and patient perspectives. Int J Chronic Obstr Pulm Dis 2013, 8:117-125.
56. van Noord J.A., Buhl R., Laforce C., Martin C., Jones F., Dolker M., et al. QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease. Thorax 2010, 65:1086-1091.
57. Yu A.P., Guerin A., Ponce de Leon D., Ramakrishnan K., Wu E.Q., Mocarski M., et al. Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers. J Med Econ 2011, 14:486-496.
58. Kerstjens H.A., Disse B., Schroder-Babo W., Bantje T.A., Gahlemann M., Sigmund R., et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J Allergy Clin Immunol 2011, 128:308-314.
59. Wong W., Scott J.D. AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 2004, 5:959-970.
60. Kritzer M.D., Li J., Dodge-Kafka K., KapilOff M.S. AKAPs: the architectural underpinnings of local cAMP signaling. J Mol Cell Cardiol 2012, 52:351-358.
61. Tröger J., Moutty M.C., Skroblin P., Klussmann E. A-kinase anchoring proteins as potential drug targets. Br J Pharmacol 2012, 166:420-433.
62. Scott J.D., Dessauer C.W., Taskén K. Creating order from chaos: cellular regulation by kinase anchoring. Annu Rev Pharmacol Toxicol 2013, 53:187-210.
63. Dodge K.L., Khouangsathiene S., KapilOff M.S., Mouton R., Hill E.V., Houslay M.D., et al. mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J 2001, 20:1921-1930.
64. Lynch M.J., Baillie G.S., Mohamed A., Li X., Maisonneuve C., Klussmann E., et al. RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells. J Biol Chem 2005, 280:33178-33189.
65. Tasken K.A., Collas P., Kemmner W.A., Witczak O., Conti M., Tasken K. Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area. J Biol Chem 2001, 276:21999-22002.
66. Horvat S.J., Deshpande D.A., Yan H., Panettieri R.A., Codina J., DuBose T.D., et al. A-kinase anchoring proteins regulate compartmentalized cAMP signaling in airway smooth muscle. FASEB J - Off Publ Fed Am Soc Exp Biology 2012, 26:3670-3679.
67. Dodge-Kafka K.L., Soughayer J., Pare G.C., Carlisle Michel J.J., Langeberg L.K., KapilOff M.S., et al. The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature 2005, 437:574-578.
68. McGraw D.W., Almoosa K.F., Paul R.J., Kobilka B.K., Liggett S.B. Antithetic regulation by beta-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway beta-agonist paradox. J Clin Invest 2003, 112:619-626.
69. Wang W.C., Schillinger R.M., Malone M.M., Liggett S.B. Paradoxical attenuation of beta2-AR function in airway smooth muscle by Gi-mediated counterregulation in transgenic mice overexpressing type 5 adenylyl cyclase. Am J Physiol Lung Cell Mol physiology 2011, 300:L472-L478.
70. Billington C.K., Hall I.P. Novel cAMP signalling paradigms: therapeutic implications for airway disease. Br J Pharmacol 2012, 166:401-410.
71. Billington C.K., Le Jeune I.R., Young K.W., Hall I.P. A major functional role for phosphodiesterase 4D5 in human airway smooth muscle cells. Am J Respir Cell Mol Biol 2008, 38:1-7.
72. Hansen G., Jin S., Umetsu D.T., Conti M. Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D. Proc Natl Acad Sci U S A 2000, 97:6751-6756.
73. Halayko A.J., Amrani Y. Mechanisms of inflammation-mediated airway smooth muscle plasticity and airways remodeling in asthma. Respir Physiol Neurobiol 2003, 137:209-222.
74. Wright D.B., Trian T., Siddiqui S., Pascoe C.D., Johnson J.R., Dekkers B.G., et al. Phenotype modulation of airway smooth muscle in asthma. Pulm Pharmacol Ther 2013, 26:42-49.
75. Ammit A.J., Hoffman R.K., Amrani Y., Lazaar A.L., Hay D.W., Torphy T.J., et al. Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth-muscle cells. Modulation by cyclic adenosine monophosphate. Am J Respir Cell Mol Biol 2000, 23:794-802.
76. Pang L., Knox A.J. Synergistic inhibition by beta(2)-agonists and corticosteroids on tumor necrosis factor-alpha-induced interleukin-8 release from cultured human airway smooth-muscle cells. Am J Respir Cell Mol Biol 2000, 23:79-85.
77. Bingham J., Sudarsanam S., Srinivasan S. Profiling human phosphodiesterase genes and splice isoforms. Biochem Biophys Res Commun 2006, 350:25-32.
78. Mehats C., Jin S.L., Wahlstrom J., Law E., Umetsu D.T., Conti M. PDE4D plays a Crit role in the control of airway smooth muscle contraction. FASEB J - Off Publ Fed Am Soc Exp Biol 2003, 17:1831-1841.
79. Torphy T.J., Undem B.J., Cieslinski L.B., Luttmann M.A., Reeves M.L., Hay D.W. Identification, characterization and functional role of phosphodiesterase isozymes in human airway smooth muscle. J Pharmacol Exp Ther 1993, 265:1213-1223.
80. Burgess J.K., Oliver B.G., Poniris M.H., Ge Q., Boustany S., Cox N., et al. A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro. J allergy Clin Immunol 2006, 118:649-657.
81. Trian T., Burgess J.K., Niimi K., Moir L.M., Ge Q., Berger P., et al. beta2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D. PloS one 2011, 6:e20000.
82. Niimi K., Ge Q., Moir L.M., Ammit A.J., Trian T., Burgess J.K., et al. beta2-Agonists upregulate PDE4 mRNA but not protein or activity in human airway smooth muscle cells from asthmatic and nonasthmatic volunteers. Am J Physiol Lung Cell Mol Physiol 2012, 302:L334-L342.
83. Himes B.E., Hunninghake G.M., Baurley J.W., Rafaels N.M., Sleiman P., Strachan D.P., et al. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am J Hum Genet 2009, 84:581-593.
84. Bundschuh D.S., Eltze M., Barsig J., Wollin L., Hatzelmann A., Beume R. In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J Pharmacol Exp Ther 2001, 297:280-290.
85. Rabe K.F., Tenor H., Dent G., Schudt C., Liebig S., Magnussen H. Phosphodiesterase isozymes modulating inherent tone in human airways: identification and characterization. Am J Physiol 1993, 264:L458-L464.
86. Schmidt D.T., Watson N., Dent G., Ruhlmann E., Branscheid D., Magnussen H., et al. The effect of selective and non-selective phosphodiesterase inhibitors on allergen- and leukotriene C(4)-induced contractions in passively sensitized human airways. Br J Pharmacol 2000, 131:1607-1618.
87. Goncharova E.A., Billington C.K., Irani C., Vorotnikov A.V., Tkachuk V.A., Penn R.B., et al. Cyclic AMP-mobilizing agents and glucocorticoids modulate human smooth muscle cell migration. Am J Respir Cell Mol Biol 2003, 29:19-27.
88. Mata M., Martinez I., Melero J.A., Tenor H., Cortijo J. Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells. PloS one 2013, 8:e69670.
89. Kobayashi M., Kubo S., Shiraki K., Iwata M., Hirano Y., Ohtsu Y., et al. Therapeutic potential of ASP3258, a selective phosphodiesterase 4 inhibitor, on chronic eosinophilic airway inflammation. Pharmacology 2012, 90:223-232.
90. Gauvreau G.M., Boulet L.P., Schmid-Wirlitsch C., Cote J., Duong M., Killian K.J., et al. Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects. Respir Res 2011, 12:140.
91. Rennard S., Knobil K., Rabe K.F., Morris A., Schachter N., Locantore N., et al. The efficacy and safety of cilomilast in COPD. Drugs 2008, 68(Suppl 2):3-57.
92. Martorana P.A., Beume R., Lucattelli M., Wollin L., Lungarella G. Roflumilast fully prevents emphysema in mice chronically exposed to cigarette smoke. Am J Respir Crit Care Med 2005, 172:848-853.
93. Martorana P.A., Lunghi B., Lucattelli M., De Cunto G., Beume R., Lungarella G. Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice. BMC Pulm Med 2008, 8:17.
94. Milara J., Armengot M., Banuls P., Tenor H., Beume R., Artigues E., et al. Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro. Br J Pharmacol 2012, 166:2243-2262.
95. Rabe K.F., Bateman E.D., O'Donnell D., Witte S., Bredenbroker D., Bethke T.D. Roflumilast-an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2005, 366:563-571.
96. Yu T., Fain K., Boyd C.M., Singh S., Weiss C.O., Li T., et al. Benefits and harms of roflumilast in moderate to severe COPD. Thorax 2013, 69:616-622.
97. Chong J., Leung B., Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013, 11:CD002309.
98. Nials A.T., Tralau-Stewart C.J., Gascoigne M.H., Ball D.I., Ranshaw L.E., Knowles R.G. In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitor. J Pharmacol Exp Ther 2011, 337:137-144.
99. Caterina M.J., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D., Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389:816-824.
100. Ramsey I.S., Delling M., Clapham D.E. An introduction to TRP channels. Annu Rev Physiol 2006, 68:619-647.
101. Clapham D.E. TRP channels as cellular sensors. Nature 2003, 426:517-524.
102. Banner K.H., Igney F., Poll C. TRP channels: emerging targets for respiratory disease. Pharmacol Ther 2011, 130:371-384.
103. Prasad P., Yanagihara A.A., Small-Howard A.L., Turner H., Stokes A.J. Secretogranin III directs secretory vesicle biogenesis in mast cells in a manner dependent upon interaction with chromogranin A. J Immunol 2008, 181:5024-5034.
104. Bautista D.M., Jordt S.E., Nikai T., Tsuruda P.R., Read A.J., Poblete J., et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 2006, 124:1269-1282.
105. Story G.M., Peier A.M., Reeve A.J., Eid S.R., Mosbacher J., Hricik T.R., et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 2003, 112:819-829.
106. Bandell M., Story G.M., Hwang S.W., Viswanath V., Eid S.R., Petrus M.J., et al. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 2004, 41:849-857.
107. Jang Y., Lee Y., Kim S.M., Yang Y.D., Jung J., Oh U. Quantitative analysis of TRP channel genes in mouse organs. Archiv Pharmacal Res 2012, 35:1823-1830.
108. Nassenstein C., Kwong K., Taylor-Clark T., Kollarik M., Macglashan D.M., Braun A., et al. Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Physiol 2008, 586:1595-1604.
109. Kunert-Keil C., Bisping F., Kruger J., Brinkmeier H. Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics 2006, 7:159.
110. Grant A., Amadesi S., Bunnett N.W. Protease-Activated receptors: mechanisms by which proteases sensitize TRPV channels to induce neurogenic inflammation and pain. TRP ion channel function in sensory transduction and cellular signaling cascades 2007, Boca Raton (FL). W.B. Liedtke, S. Heller (Eds.).
111. Jia Y., Wang X., Varty L., Rizzo C.A., Yang R., Correll C.C., et al. Functional TRPV4 channels are expressed in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2004, 287:L272-L278.
112. Alvarez D.F., King J.A., Weber D., Addison E., Liedtke W., Townsley M.I. Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury. Circ Res 2006, 99:988-995.
113. Dietrich A., Chubanov V., Kalwa H., Rost B.R., Gudermann T. Cation channels of the transient receptor potential superfamily: their role in physiological and pathophysiological processes of smooth muscle cells. Pharmacol Ther 2006, 112:744-760.
114. Yang X.R., Lin M.J., McIntosh L.S., Sham J.S. Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol 2006, 290:L1267-L1276.
115. Peier A.M., Moqrich A., Hergarden A.C., Reeve A.J., Andersson D.A., Story G.M., et al. A TRP channel that senses cold stimuli and menthol. Cell 2002, 108:705-715.
116. Li M., Li Q., Yang G., Kolosov V.P., Perelman J.M., Zhou X.D. Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism. J Allergy Clin Immunol 2011, 128. 626-34 e1-5.
117. Heiner I., Eisfeld J., Halaszovich C.R., Wehage E., Jungling E., Zitt C., et al. Expression profile of the transient receptor potential (TRP) family in neutrophil granulocytes: evidence for currents through long TRP channel 2 induced by ADP-ribose and NAD. Biochem J 2003, 371:1045-1053.
118. Li S., Westwick J., Poll C. Transient receptor potential (TRP) channels as potential drug targets in respiratory disease. Cell Calcium 2003, 33:551-558.
119. McMeekin S.R., Dransfield I., Rossi A.G., Haslett C., Walker T.R. E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils. Blood 2006, 107:4938-4945.
120. Finney-Hayward T.K., Popa M.O., Bahra P., Li S., Poll C.T., Gosling M., et al. Expression of transient receptor potential C6 channels in human lung macrophages. Am J Respir Cell Mol Biol 2010, 43:296-304.
121. Liedtke W., Choe Y., Marti-Renom M.A., Bell A.M., Denis C.S., Sali A., et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 2000, 103:525-535.
122. Deering-Rice C.E., Romero E.G., Shapiro D., Hughen R.W., Light A.R., Yost G.S., et al. Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): a probable mechanism of acute pulmonary toxicity for DEP. Chem Res Toxicol 2011, 24:950-959.
123. Shapiro D., Deering-Rice C.E., Romero E.G., Hughen R.W., Light A.R., Veranth J.M., et al. Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by wood smoke particulate material. Chem Res Toxicol 2013, 26:750-758.
124. Raemdonck K., de Alba J., Birrell M.A., Grace M., Maher S.A., Irvin C.G., et al. A role for sensory nerves in the late asthmatic response. Thorax 2012, 67:19-25.
125. Andre E., Campi B., Materazzi S., Trevisani M., Amadesi S., Massi D., et al. Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest 2008, 118:2574-2582.
126. Hox V., Vanoirbeek J.A., Alpizar Y.A., Voedisch S., Callebaut I., Bobic S., et al. Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice. Am J Respir Crit Care Med 2013, 187:486-493.
127. Caceres A.I., Brackmann M., Elia M.D., Bessac B.F., del Camino D., D'Amours M., et al. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci U S A 2009, 106:9099-9104.
128. Spiess P.C., Kasahara D., Habibovic A., Hristova M., Randall M.J., Poynter M.E., et al. Acrolein exposure suppresses antigen-induced pulmonary inflammation. Respir Res 2013, 14:107.
129. Belvisi M.G., Miura M., Stretton D., Barnes P.J. Capsazepine as a selective antagonist of capsaicin-induced activation of C-fibres in guinea-pig bronchi. Eur J Pharmacol 1992, 215:341-344.
130. Rehman R., Bhat Y.A., Panda L., Mabalirajan U. TRPV1 inhibition attenuates IL-13 mediated asthma features in mice by reducing airway epithelial injury. Int Immunopharmacol 2013, 15:597-605.
131. Mori T., Saito K., Ohki Y., Arakawa H., Tominaga M., Tokuyama K. Lack of transient receptor potential vanilloid-1 enhances Th2-biased immune response of the airways in mice receiving intranasal, but not intraperitoneal, sensitization. Int Arch Allergy Immunol 2011, 156:305-312.
132. Zhu G., Investigators I., Gulsvik A., Bakke P., Ghatta S., Anderson W., et al. Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease. Hum Mol Genet 2009, 18:2053-2062.
133. Costa S.K., Kumagai Y., Brain S.D., Teixeira S.A., Varriano A.A., Barreto M.A., et al. Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ). Arch Toxicol 2010, 84:109-117.
134. Keatings V.M., Jatakanon A., Worsdell Y.M., Barnes P.J. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med 1997, 155:542-548.
135. Damann N., Owsianik G., Li S., Poll C., Nilius B. The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils. Acta physiol 2009, 195:3-11.
136. Sethi J.M., Rochester C.L. Smoking and chronic obstructive pulmonary disease. Clin chest Med 2000, 21:67-86. viii.
137. Facchinetti F., Amadei F., Geppetti P., Tarantini F., Di Serio C., Dragotto A., et al. Alpha,beta-unsaturated aldehydes in cigarette smoke release inflammatory mediators from human macrophages. Am J Respir Cell Mol Biol 2007, 37:617-623.
138. Gylling H., Vanhanen H., Miettinen T.A. Hypolipidemic effect and mechanism of ketoconazole without and with cholestyramine in familial hypercholesterolemia. Metabolism - Clin Exp 1991, 40:35-41.
139. Lin Y.S., Hsu C.C., Bien M.Y., Hsu H.C., Weng H.T., Kou Y.R. Activations of TRPA1 and P2X receptors are important in ROS-mediated stimulation of capsaicin-sensitive lung vagal afferents by cigarette smoke in rats. J Appl Physiol 2010, 108:1293-1303.
140. Nassini R., Materazzi S., De Siena G., De Cesaris F., Geppetti P. Transient receptor potential channels as novel drug targets in respiratory diseases. Curr Opin Invest Drugs 2010, 11:535-542.
141. Tsuji F., Murai M., Oki K., Inoue H., Sasano M., Tanaka H., et al. Effects of SA13353, a transient receptor potential vanilloid 1 agonist, on leukocyte infiltration in lipopolysaccharide-induced acute lung injury and ovalbumin-induced allergic airway inflammation. J Pharmacol Sci 2010, 112:487-490.
142. Baxter M., Birrell M., Belvisi M. The role of transient receptor potential vanilloid 1 (TRPV1) Tobacco Smoke Induced Airway Inflammation. Am Thorac Soc. 2012, p. A6410-A.
143. Fuller R.W., Dixon C.M., Barnes P.J. Bronchoconstrictor response to inhaled capsaicin in humans. J Appl Physiol 1985, 58:1080-1084.
144. Lalloo U.G., Fox A.J., Belvisi M.G., Chung K.F., Barnes P.J. Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs. J Appl Physiol 1995, 79:1082-1087.
145. Bonvini S., Adcock J., Grace M., Baker K., Birrell M., MG B Activation of TRPV4 causes bronchoconstriction: a possible role in respiratory disease?. Eur Respir J 2013, p. Abstract 1759.
146. Barnes P.J. The pharmacological properties of tiotropium. Chest 2000, 117:63S-66S.
147. Nasra J., Belvisi M.G. Modulation of sensory nerve function and the cough reflex: understanding disease pathogenesis. Pharmacol Ther 2009, 124:354-375.
148. Young E.C., Smith J.A. Pharmacologic therapy for cough. Curr Opin Pharmacol 2011, 11:224-230.
149. French C.L., Irwin R.S., Curley F.J., Krikorian C.J. Impact of chronic cough on quality of life. Arch Intern Med 1998, 158:1657-1661.
150. Canning B.J. Anatomy and neurophysiology of the cough reflex: ACCP evidence-based clinical practice guidelines. Chest 2006, 129:33S-47S.
151. Ford A.C., Forman D., Moayyedi P., Morice A.H. Cough in the community: a cross sectional survey and the relationship to gastrointestinal symptoms. Thorax 2006, 61:975-979.
152. Watanabe N., Horie S., Michael G.J., Keir S., Spina D., Page C.P., et al. Immunohistochemical co-localization of transient receptor potential vanilloid (TRPV)1 and sensory neuropeptides in the guinea-pig respiratory system. Neuroscience 2006, 141:1533-1543.
153. Doherty M.J., Mister R., Pearson M.G., Calverley P.M. Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary disease. Thorax 2000, 55:643-649.
154. O'Connell F., Thomas V.E., Studham J.M., Pride N.B., Fuller R.W. Capsaicin cough sensitivity increases during upper respiratory infection. Respir Med 1996, 90:279-286.
155. Higenbottam T. Chronic cough and the cough reflex in common lung diseases. Pulm Pharmacol Ther 2002, 15:241-247.
156. Karlsson J.A., Zackrisson C., Lundberg J.M. Hyperresponsiveness to tussive stimuli in cigarette smoke-exposed guinea-pigs: a role for capsaicin-sensitive, calcitonin gene-related peptide-containing nerves. Acta Physiol Scand 1991, 141:445-454.
157. Lewis C.A., Ambrose C., Banner K., Battram C., Butler K., Giddings J., et al. Animal models of cough: literature review and presentation of a novel cigarette smoke-enhanced cough model in the guinea-pig. Pulm Pharmacol Ther 2007, 20:325-333.
158. Maher S.A., Belvisi M.G. Prostanoids and the cough reflex. Lung 2010, 188(Suppl. 1):S9-S12.
159. Grace M.S., Belvisi M.G. TRPA1 receptors in cough. Pulm Pharmacol Ther 2011, 24:286-288.
160. Birrell M.A., Belvisi M.G., Grace M., Sadofsky L., Faruqi S., Hele D.J., et al. TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med 2009, 180:1042-1047.
161. Belvisi M., Bonvini S., Grace M., Ching Y., Dubuis E., Adcock J., et al. Activation of airway sensory nerves: a key role for the TRPV4 channel. Am Thorac Soc 2013, p. A5265-A.
162. Blease K. Targeting kinases in asthma. . Expert Opin Investig Drugs 2005, 14:1213-1220.
163. Duan W., Wong W.S. Targeting mitogen-activated protein kinases for asthma. Curr Drug Targets 2006, 7:691-698.
164. Underwood D.C., Osborn R.R., Kotzer C.J., Adams J.L., Lee J.C., Webb E.F., et al. SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence. J Pharmacol Exp Ther 2000, 293:281-288.
165. Liang L., Li F., Bao A., Zhang M., Chung K.F., Zhou X. Activation of p38 mitogen-activated protein kinase in ovalbumin and ozone-induced mouse model of asthma. Respirology 2013, 18(Suppl 3):20-29.
166. Duan W., Chan J.H., Wong C.H., Leung B.P., Wong W.S. Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J Immunol 2004, 172:7053-7059.
167. Alrashdan Y.A., Alkhouri H., Chen E., Lalor D.J., Poniris M., Henness S., et al. Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement. Am J Physiol Lung Cell Mol Physiol 2012, 302:L1118-L1127.
168. Eynott P.R., Xu L., Bennett B.L., Noble A., Leung S.Y., Nath P., et al. Effect of an inhibitor of Jun N-terminal protein kinase, SP600125, in single allergen challenge in sensitized rats. Immunology 2004, 112:446-453.
169. Ito K., Caramori G., Adcock I.M. Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease. J Pharmacol Exp Ther 2007, 321:1-8.
170. Finan P.M., Thomas M.J. PI 3-kinase inhibition: a therapeutic target for respiratory disease. Biochem Soc Trans 2004, 32:378-382.
171. Kampe M., Lampinen M., Stolt I., Janson C., Stalenheim G., Carlson M. PI3-kinase regulates eosinophil and neutrophil degranulation in patients with allergic rhinitis and allergic asthma irrespective of allergen challenge model. Inflammation 2012, 35:230-239.
172. Duan W., Aguinaldo Datiles A.M., Leung B.P., Vlahos C.J., Wong W.S. An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model. Int Immunopharmacol 2005, 5:495-502.
173. Moir L.M., Trian T., Ge Q., Shepherd P.R., Burgess J.K., Oliver B.G., et al. Phosphatidylinositol 3-kinase isoform-specific effects in airway mesenchymal cell function. J Pharmacol Exp Ther 2011, 337:557-566.
174. Ge Q., Moir L.M., Trian T., Niimi K., Poniris M., Shepherd P.R., et al. The phosphoinositide 3'-kinase p110delta modulates contractile protein production and IL-6 release in human airway smooth muscle. J Cell Physiol 2012, 227:3044-3052.
175. Krymskaya V.P., Penn R.B., Orsini M.J., Scott P.H., Plevin R.J., Walker T.R., et al. Phosphatidylinositol 3-kinase mediates mitogen-induced human airway smooth muscle cell proliferation. Am J Physiol 1999, 277:L65-L78.
176. Kume H. RhoA/Rho-kinase as a therapeutic target in asthma. Curr Med Chem 2008, 15:2876-2885.
177. Schaafsma D., Gosens R., Zaagsma J., Halayko A.J., Meurs H. Rho kinase inhibitors: a novel therapeutical intervention in asthma?. Eur J Pharmacol 2008, 585:398-406.
178. Wettschureck N., Offermanns S. Rho/Rho-kinase mediated signaling in physiology and pathophysiology. J Mol Med 2002, 80:629-638.
179. Aihara M., Dobashi K., Iizuka K., Nakazawa T., Mori M. Effect of Y-27632 on release of cytokines from peripheral T cells in asthmatic patients and normal subjects. Int Immunopharmacol 2004, 4:557-561.
180. Yoshii A., Iizuka K., Dobashi K., Horie T., Harada T., Nakazawa T., et al. Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization. Am J Respir Cell Mol Biol 1999, 20:1190-1200.
181. Schaafsma D., Bos I.S., Zuidhof A.B., Zaagsma J., Meurs H. Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction. Respir Res 2006, 7:121.
182. Hashimoto K., Peebles R.S., Sheller J.R., Jarzecka K., Furlong J., Mitchell D.B., et al. Suppression of airway hyperresponsiveness induced by ovalbumin sensitisation and RSV infection with Y-27632, a Rho kinase inhibitor. Thorax 2002, 57:524-527.
183. Henry P.J., Mann T.S., Goldie R.G. A rho kinase inhibitor, Y-27632 inhibits pulmonary eosinophilia, bronchoconstriction and airways hyperresponsiveness in allergic mice. Pulm Pharmacol Ther 2005, 18:67-74.
184. Wu F.Q., Zhu S.Y., He C.X., Gu M.X. Effects of fasudil on the expression of Rho kinase-1 and airway inflammation in a mouse model of asthma. Zhonghua Jie He He Hu Xi Za Zhi - Chin J Tuberc Respir Dis 2009, 32:847-849.
185. Taki F., Kume H., Kobayashi T., Ohta H., Aratake H., Shimokata K. Effects of Rho-kinase inactivation on eosinophilia and hyper-reactivity in murine airways by allergen challenges. Clin Exp Allergy - J Br Soc Allergy Clin Immunol 2007, 37:599-607.
186. Renda T., Baraldo S., Pelaia G., Bazzan E., Turato G., Papi A., et al. Increased activation of p38 MAPK in COPD. Eur Respir J - Off J Eur Soc Clin Respir Physiol 2008, 31:62-69.
187. Huang C., Xie M., He X., Gao H. Activity of sputum p38 MAPK is correlated with airway inflammation and reduced FEV1 in COPD patients. Med Sci Monit Int Med J Exp Clin Res 2013, 19:1229-1235.
188. Amano H., Murata K., Matsunaga H., Tanaka K., Yoshioka K., Kobayashi T., et al. p38 mitogen-activated protein kinase accelerates emphysema in mouse model of chronic obstructive pulmonary disease. J Recept signal Transduct Res 2014.
189. Medicherla S., Fitzgerald M.F., Spicer D., Woodman P., Ma J.Y., Kapoun A.M., et al. p38alpha-selective mitogen-activated protein kinase inhibitor SD-282 reduces inflammation in a subchronic model of tobacco smoke-induced airway inflammation. J Pharmacol Exp Ther 2008, 324:921-929.
190. Singh D., Smyth L., Borrill Z., Sweeney L., Tal-Singer R. A randomized, placebo-controlled study of the effects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of inflammation in COPD patients. J Clin Pharmacol 2010, 50:94-100.
191. Duvoix A., Dickens J., Haq I., Mannino D., Miller B., Tal-Singer R., et al. Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease. Thorax 2013, 68:670-676.
192. Lomas D.A., Lipson D.A., Miller B.E., Willits L., Keene O., Barnacle H., et al. An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Pharmacol 2012, 52:416-424.
193. Watz H., Barnacle H., Hartley B.F., Chan R. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014, 2:63-72.
194. MacNee W., Allan R.J., Jones I., De Salvo M.C., Tan L.F. Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax 2013, 68:738-745.
195. Millan D.S., Bunnage M.E., Burrows J.L., Butcher K.J., Dodd P.G., Evans T.J., et al. Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J Med Chem 2011, 54:7797-7814.
196. Fleischmann R., Kremer J., Cush J., Schulze-Koops H., Connell C.A., Bradley J.D., et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl J Med 2012, 367:495-507.
197. Fleischmann R., Cutolo M., Genovese M.C., Lee E.B., Kanik K.S., Sadis S., et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum 2012, 64:617-629.
198. Kawalec P., Mikrut A., Wisniewska N., Pilc A. The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol 2013, 32:1415-1424.
199. Sandborn W.J., Ghosh S., Panes J., Vranic I., Su C., Rousell S., et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N. Engl J Med 2012, 367:616-624.
200. To Y., Ito K., Kizawa Y., Failla M., Ito M., Kusama T., et al. Targeting phosphoinositide-3-kinase-delta with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010, 182:897-904.
201. Marwick J.A., Caramori G., Casolari P., Mazzoni F., Kirkham P.A., Adcock I.M., et al. A role for phosphoinositol 3-kinase delta in the impairment of glucocorticoid responsiveness in patients with chronic obstructive pulmonary disease. J allergy Clin Immunol 2010, 125:1146-1153.
202. Medina-Tato D.A., Ward S.G., Watson M.L. Phosphoinositide 3-kinase signalling in lung disease: leucocytes and beyond. Immunology 2007, 121:448-461.
203. Doukas J., Eide L., Stebbins K., Racanelli-Layton A., Dellamary L., Martin M., et al. Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic candidate for asthma and chronic obstructive pulmonary disease. J Pharmacol Exp Ther 2009, 328:758-765.
204. Sodergren S.C., White A., Efficace F., Sprangers M., Fitzsimmons D., Bottomley A., et al. Systematic review of the side effects associated with tyrosine kinase inhibitors used in the treatment of gastrointestinal stromal tumours on behalf of the EORTC Quality of Life Group. Crit Rev Oncol/Hematol 2014, 91:35-46.
205. Wang Z.X., Sun J., Howell C.E., Zhou Q.Y., He Z.X., Yang T., et al. Prediction of the likelihood of drug interactions with kinase inhibitors based on in vitro and computational studies. Fundam Clin Pharmacol 2014.
206. Litonjua A.A., Weiss S.T. Is vitamin D deficiency to blame for the asthma epidemic?. J Allergy Clin Immunol 2007, 120:1031-1035.
207. Chinellato I., Piazza M., Sandri M., Peroni D., Piacentini G., Boner A.L. Vitamin D serum levels and markers of asthma control in Italian children. J Pediatr 2010, 158:437-441.
208. Brehm J.M., Celedon J.C., Soto-Quiros M.E., Avila L., Hunninghake G.M., Forno E., et al. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med 2009, 179:765-771.
209. Gupta A., Sjoukes A., Richards D., Banya W., Hawrylowicz C., Bush A., et al. Relationship between serum vitamin D, disease severity and airway remodeling in children with asthma. Am J Respir Crit Care Med 2011, 201107-1239OC.
210. Brehm J.M., Schuemann B., Fuhlbrigge A.L., Hollis B.W., Strunk R.C., Zeiger R.S., et al. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol 2010, 126:52-58. e5.
211. Camargo C.A., Rifas-Shiman S.L., Litonjua A.A., Rich-Edwards J.W., Weiss S.T., Gold D.R., et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007, 85:788-795.
212. Devereux G., Litonjua A.A., Turner S.W., Craig L.C., McNeill G., Martindale S., et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr 2007, 85:853-859.
213. Erkkola M., Kaila M., Nwaru B.I., Kronberg-Kippila C., Ahonen S., Nevalainen J., et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp allergy - J Br Soc Allergy Clin Immunol 2009, 39:875-882.
214. Hypponen E., Sovio U., Wjst M., Patel S., Pekkanen J., Hartikainen A.L., et al. Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Ann N. Y Acad Sci 2004, 1037:84-95.
215. Pike K.C., Inskip H.M., Robinson S., Lucas J.S., Cooper C., Harvey N.C., et al. Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes. Thorax 2012, 67:950-956.
216. Gale C.R., Robinson S.M., Harvey N.C., Javaid M.K., Jiang B., Martyn C.N., et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 2008, 62:68-77.
217. Damera G., Fogle H.W., Lim P., Goncharova E.A., Zhao H., Banerjee A., et al. Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1. Br J Pharmacol 2009, 158:1429-1441.
218. Gorman S., Weeden C.E., Tan D.H.W., Scott N.M., Hart J., Foong R.E., et al. Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease. PloS one 2013, 8. e67823.
219. Topilski I., Flaishon L., Naveh Y., Harmelin A., Levo Y., Shachar I. The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. Eur J Immunol 2004, 34:1068-1076.
220. Matheu V., Back O., Mondoc E., Issazadeh-Navikas S. Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease. J allergy Clin Immunol 2003, 112:585-592.
221. Taher Y.A., van Esch B.C.A.M., Hofman G.A., Henricks P.A.J., van Oosterhout A.J.M. 1α,25-Dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J Immunol 2008, 180:5211-5221.
222. Xystrakis E., Kusumakar S., Boswell S., Peek E., Urry Z., Richards D.F., et al. Reversing the defective induction of IL-10â€"secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 2006, 116:146-155.
223. Searing D.A., Zhang Y., Murphy J.R., Hauk P.J., Goleva E., Leung D.Y. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. J Allergy Clin Immunol 2010, 125:995-1000.
224. Janssens W., Bouillon R., Claes B., Carremans C., Lehouck A., Buysschaert I., et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax 2010, 65:215-220.
225. Persson L.J.P., Aanerud M., Hiemstra P.S., Hardie J.A., Bakke P.S., Eagan T.M.L. Chronic obstructive pulmonary disease is associated with Low levels of vitamin D. PloS one 2012, 7. e38934.
226. Hornikx M., Van Remoortel H., Lehouck A., Mathieu C., Maes K., Gayan-Ramirez G., et al. Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trial. Respir Res 2012, 13:84.
227. Bjerk S.M., Edgington B.D., Rector T.S., Kunisaki K.M. Supplemental vitamin D and physical performance in COPD: a pilot randomized trial. Int J Chronic Obstr Pulm Dis 2013, 8:97-104.
228. Shaheen S.O., Jameson K.A., Robinson S.M., Boucher B.J., Syddall H.E., Sayer A.A., et al. Relationship of vitamin D status to adult lung function and COPD. Thorax 2011, 66:692-698.
229. Wood A., Bassford C., Webster D., Newby P., Rajesh P., Stockley R. Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages. Thorax 2011, 66:205-210.
230. Black P.N., Scragg R. Relationship between serum 25-Hydroxyvitamin D and pulmonary function in the Third National health and Nutrition Examination Survey. Chest 2005, 128:3792-3798.
231. Zosky G.R., Berry L.J., Elliot J.G., James A.L., Gorman S., Hart P.H. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Respir Crit Care Med 2011, 183:1336-1343.
232. Sundar I.K., Hwang J.-W., Wu S., Sun J., Rahman I. Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation. Biochem Biophys Res Commun 2011, 406:127-133.
233. Jimenez-Morales S., Martinez-Aguilar N., Gamboa-Becerra R., Jimenez-Ruiz J.L., Lopez-Ley D., Lou H., et al. Polymorphisms in metalloproteinase-9 are associated with the risk for asthma in Mexican pediatric patients. Hum Immunol 2013, 74:998-1002.
234. Hong Z., Lin Y.M., Qin X., Peng J.L. Serum MMP-9 is elevated in children with asthma. Mol Med Rep 2012, 5:462-464.
235. Mattos W., Lim S., Russell R., Jatakanon A., Chung K.F., Barnes P.J. Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest 2002, 122:1543-1552.
236. Ko F.W., Diba C., Roth M., McKay K., Johnson P.R., Salome C., et al. A comparison of airway and serum matrix metalloproteinase-9 activity among normal subjects, asthmatic patients, and patients with asthmatic mucus hypersecretion. Chest 2005, 127:1919-1927.
237. Hoshino M., Nakamura Y., Sim J., Shimojo J., Isogai S. Bronchial subepithelial fibrosis and expression of matrix metalloproteinase-9 in asthmatic airway inflammation. J allergy Clin Immunol 1998, 102:783-788.
238. Cataldo D., Munaut C., Noel A., Frankenne F., Bartsch P., Foidart J.M., et al. MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol 2000, 123:259-267.
239. Hirakawa S., Kojima T., Obata K., Okabayashi T., Yokota S., Nomura K., et al. Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells. J Med Virol 2013, 85:2141-2150.
240. Gueders M.M., Bertholet P., Perin F., Rocks N., Maree R., Botta V., et al. A novel formulation of inhaled doxycycline reduces allergen-induced inflammation, hyperresponsiveness and remodeling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma. Biochem Pharmacol 2008, 75:514-526.
241. Lee K.S., Jin S.M., Kim S.S., Lee Y.C. Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate-induced asthma. J Allergy Clin Immunol 2004, 113:902-909.
242. Leemans J., Kirschvink N., Clercx C., Snaps F., Gustin P. Effect of short-term oral and inhaled corticosteroids on airway inflammation and responsiveness in a feline acute asthma model. Veterinary J 2012, 192:41-48.
243. Mukhopadhyay S., Sypek J., Tavendale R., Gartner U., Winter J., Li W., et al. Matrix metalloproteinase-12 is a therapeutic target for asthma in children and young adults. J Allergy Clin Immunol 2010, 126:70-76. e16.
244. Li W., Li J., Wu Y., Wu J., Hotchandani R., Cunningham K., et al. A selective matrix metalloprotease 12 inhibitor for potential treatment of chronic obstructive pulmonary disease (COPD): discovery of (S)-2-(8-(methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408). J Med Chem 2009, 52:1799-1802.
245. Gueders M.M., Balbin M., Rocks N., Foidart J.M., Gosset P., Louis R., et al. Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J Immunol 2005, 175:2589-2597.
246. D'Armiento J.M., Goldklang M.P., Hardigan A.A., Geraghty P., Roth M.D., Connett J.E., et al. Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema. PloS one 2013, 8. e56352.
247. Culpitt S.V., Rogers D.F., Traves S.L., Barnes P.J., Donnelly L.E. Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma. Respir Med 2005, 99:703-710.
248. Segura-Valdez L., Pardo A., Gaxiola M., Uhal B.D., Becerril C., Selman M. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 2000, 117:684-694.
249. Demedts I.K., Morel-Montero A., Lebecque S., Pacheco Y., Cataldo D., Joos G.F., et al. Elevated MMP-12 protein levels in induced sputum from patients with COPD. Thorax 2006, 61:196-201.
250. Mercer P.F., Shute J.K., Bhowmik A., Donaldson G.C., Wedzicha J.A., Warner J.A. MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation. Respir Res 2005, 6:151.
251. Kwiatkowska S., Noweta K., Zieba M., Nowak D., Bialasiewicz P. Enhanced exhalation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in patients with COPD exacerbation: a prospective study. Respir Int Rev Thorac Dis 2012, 84:231-241.
252. Ilumets H., Rytila P., Demedts I., Brusselle G.G., Sovijarvi A., Myllarniemi M., et al. Matrix metalloproteinases -8, -9 and -12 in smokers and patients with stage 0 COPD. Int J Chronic Obstr Pulm Dis 2007, 2:369-379.
253. Imai K., Dalal S.S., Chen E.S., Downey R., Schulman L.L., Ginsburg M., et al. Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema. Am J Respir Crit Care Med 2001, 163:786-791.
254. Geraghty P., Dabo A.J., D'Armiento J. TLR4 protein contributes to cigarette smoke-induced matrix metalloproteinase-1 (MMP-1) expression in chronic obstructive pulmonary disease. J Biol Chem 2011, 286:30211-30218.
255. Churg A., Wang R., Wang X., Onnervik P.O., Thim K., Wright J.L. Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs. Thorax 2007, 62:706-713.
256. Lavigne M.C., Eppihimer M.J. Cigarette smoke condensate induces MMP-12 gene expression in airway-like epithelia. Biochem Biophys Res Commun 2005, 330:194-203.
257. Bezerra F.S., Valenca S.S., Pires K.M., Lanzetti M., Pimenta W.A., Schmidt A.C., et al. Long-term exposure to cigarette smoke impairs lung function and increases HMGB-1 expression in mice. Respir Physiol Neurobiol 2011, 177:120-126.
258. Xu J., Xu F., Lin Y. Cigarette smoke synergizes lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha secretion from macrophages via substance P-mediated nuclear factor-kappaB activation. Am J Respir Cell Mol Biol 2011, 44:302-308.
259. Vlahos R., Bozinovski S., Jones J.E., Powell J., Gras J., Lilja A., et al. Differential protease, innate immunity, and NF-kappaB induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice. Am J Physiol Lung Cell Mol Physiol 2006, 290:L931-L945.
260. Churg A., Wang X., Wang R.D., Meixner S.C., Pryzdial E.L., Wright J.L. Alpha1-antitrypsin suppresses TNF-alpha and MMP-12 production by cigarette smoke-stimulated macrophages. Am J Respir Cell Mol Biol 2007, 37:144-151.
261. D'Armiento J., Dalal S.S., Okada Y., Berg R.A., Chada K. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 1992, 71:955-961.
262. Foronjy R., Nkyimbeng T., Wallace A., Thankachen J., Okada Y., Lemaitre V., et al. Transgenic expression of matrix metalloproteinase-9 causes adult-onset emphysema in mice associated with the loss of alveolar elastin. Am J Physiol Lung Cell Mol Physiol 2008, 294:L1149-L1157.
263. Churg A., Dai J., Zay K., Karsan A., Hendricks R., Yee C., et al. Alpha-1-antitrypsin and a broad spectrum metalloprotease inhibitor, RS113456, have similar acute anti-inflammatory effects. Lab Invest J Tech Methods Pathol 2001, 81:1119-1131.
264. Morris A., Kinnear G., Wan W.Y., Wyss D., Bahra P., Stevenson C.S. Comparison of cigarette smoke-induced acute inflammation in multiple strains of mice and the effect of a matrix metalloproteinase inhibitor on these responses. J Pharmacol Exp Ther 2008, 327:851-862.
265. Shiomi T., Okada Y., Foronjy R., Schiltz J., Jaenish R., Krane S., et al. Emphysematous changes are caused by degradation of type III collagen in transgenic mice expressing MMP-1. Exp Lung Res 2003, 29:1-15.
266. Dahl R., Titlestad I., Lindqvist A., Wielders P., Wray H., Wang M., et al. Effects of an oral MMP-9 and -12 inhibitor, AZD1236, on biomarkers in moderate/severe COPD: a randomised controlled trial. Pulm Pharmacol Ther 2012, 25:169-177.
267. Raffestin B., Cerrina J., Boullet C., Labat C., Benveniste J., Brink C. Response and sensitivity of isolated human pulmonary muscle preparations to pharmacological agents. J Pharmacol Exp Ther 1985, 233:186-194.
268. Van Amsterdam R.G., Meurs H., Ten Berge R.E., Veninga N.C., Brouwer F., Zaagsma J. Role of phosphoinositide metabolism in human bronchial smooth muscle contraction and in functional antagonism by beta-adrenoceptor agonists. Am Rev Respir Dis 1990, 142:1124-1128.
269. Torphy T.J., Zheng C., Peterson S.M., Fiscus R.R., Rinard G.A., Mayer S.E. Inhibitory effect of methacholine on drug-induced relaxation, cyclic AMP accumulation, and cyclic AMP-dependent protein kinase activation in canine tracheal smooth muscle. J Pharmacol Exp Ther 1985, 233:409-417.
270. Van Amsterdam R.G., Meurs H., Brouwer F., Postema J.B., Timmermans A., Zaagsma J. Role of phosphoinositide metabolism in functional antagonism of airway smooth muscle contraction by beta-adrenoceptor agonists. Eur J Pharmacol 1989, 172:175-183.
271. Novartis. , 2013. http://www.novartis.com/newsroom/media-releases/en/2013/1730580.shtml.
272. Dahl R., Chapman K.R., Rudolf M., Mehta R., Kho P., Alagappan V.K., et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Respir Med 2013, 107:1558-1567.
273. Dahl R., Jadayel D., Alagappan V.K., Chen H., Banerji D. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study. Int J Chronic Obstr Pulm Dis 2013, 8:501-508.
274. Mahler D.A., Decramer M., D'Urzo A., Worth H., White T., Alagappan V.K., et al. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur Respir J - Off J Eur Soc Clin Respir Physiol 2014, 43:1599-1609.
275. TOviTO. http://boehringer-ingelheim.com/news/news_releases/press_releases/2013/09_september_2013olodaterol.html.
276. Bouyssou T., Schanapp A., Casarosa P. Addition of the new once daily LABA BI 1744 to tiotropium results in superior bronchoprotection in pre-clinical models. American J Resp Crit Care Medicine 2010, A4448. American Thoracic Society. Barcelona.
277. Costa L., Roth M., Tamm M. Tiotropium and olodaterol exert anti-proliferative effects on pulmonary fibroblasts of asthmatic patients in vitro. Annual Congress of the European Respiratory Society. Barcelona 2013, [Abstract P571].
278. Profita M., Bonanno A., Montalbano A.M., Albano G.D., Riccobono L., Siena L., et al. Beta(2) long-acting and anticholinergic drugs control TGF-beta1-mediated neutrophilic inflammation in COPD. Biochim Biophys Acta 2012, 1822:1079-1089.
279. Costa L., Roth M., Tamm M. Tiotropium enhances the inhibitory effect of the long acting beta2-agonist olodaterol on the release of IL-6 and IL-8 by primary human lung fibroblasts of asthma patients. Annual Congress of the European Respiratory Society. Vienna 2012, [Abstract].
280. Wielders P.L., Ludwig-Sengpiel A., Locantore N., Baggen S., Chan R., Riley J.H. A new class of bronchodilator improves lung function in COPD: a trial with GSK961081. Eur Respir J Off J Eur Soc Clin Respir Physiol 2013, 42:972-981.
281. Bateman E.D., Kornmann O., Ambery C., Norris V. Pharmacodynamics of GSK961081, a bi-functional molecule, in patients with COPD. Pulm Pharmacol Ther 2013, 26:581-587.
282. Cates C.J., Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane database Syst Rev 2013, 4. CD007313.
283. Busse W.W., O'Byrne P.M., Bleecker E.R., Lotvall J., Woodcock A., Andersen L., et al. Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the beta2 agonist vilanterol administered once daily for 52 weeks in patients >=12 years old with asthma: a randomised trial. Thorax 2013, 68:513-520.
284. O'Byrne P.M., Bleecker E.R., Bateman E.D., Busse W.W., Woodcock A., Forth R., et al. Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma. Eur Respir J Off J Eur Soc Clin Respir Physiol 2014, 43:773-782.
285. Oliver A., Bjermer L., Quinn D., Saggu P., Thomas P., Yarnall K., et al. Modulation of allergen-induced bronchoconstriction by fluticasone furoate and vilanterol alone or in combination. Allergy 2013, 68:1136-1142.
286. Bollmeier S.G., Prosser T.R. Combination of fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease. Ann Pharmacother 2014, 48:250-257.
287. Snowise N.G., Clements D., Ho S.Y., Follows R.M. Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma. Curr Med Res Opin 2013, 29:1663-1674.
288. Gao J.M., Cai F., Peng M., Ma Y., Wang B. Montelukast improves air trapping, not airway remodeling, in patients with moderate-to-severe asthma: a pilot study. Chin Med J 2013, 126:2229-2234.
289. Hoshino M., Ohtawa J. Effects of tiotropium and salmeterol/fluticasone propionate on airway wall thickness in chronic obstructive pulmonary disease. Respir Int Rev Thorac Dis 2013, 86:280-287.
290. Maltais F., Mahler D.A., Pepin V., Nadreau E., Crater G.D., Morris A.N., et al. Effect of fluticasone propionate/salmeterol plus tiotropium versus tiotropium on walking endurance in COPD. Eur Respir J Off J Eur Soc Clin Respir Physiol 2013, 42:539-541.
291. Popov T.A., Petrova D., Kralimarkova T.Z., Ivanov Y., Popova T., Peneva M., et al. Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics. Pulm Pharmacol Ther 2013, 26:624-629.
292. Nakaji H., Petrova G., Matsumoto H., Iwata T., Ito I., Oguma T., et al. Effects of 24-week add-on treatment with ciclesonide and montelukast on small airways inflammation in asthma. Ann allergy, asthma & Immunol - Off Publ Am Coll Allergy, Asthma Immunol 2013, 110:198-203.
293. Timmins S.C., Diba C., Schoeffel R.E., Salome C.M., King G.G., Thamrin C. Changes in oscillatory impedance and nitrogen washout with combination fluticasone/salmeterol therapy in COPD. Respir Med 2014, 108:344-350.
294. Drake M.G., Kaufman E.H., Fryer A.D., Jacoby D.B. The therapeutic potential of Toll-like receptor 7 stimulation in asthma. Inflamm Allergy Drug Targets 2012, 11:484-491.
295. Bezemer G.F., Sagar S., van Bergenhenegouwen J., Georgiou N.A., Garssen J., Kraneveld A.D., et al. Dual role of Toll-like receptors in asthma and chronic obstructive pulmonary disease. Pharmacol Rev 2012, 64:337-358.
296. Liggett S.B. Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators. Expert Opin Ther Targets 2013, 17:721-731.
297. Sukkar M.B., Ullah M.A., Gan W.J., Wark P.A., Chung K.F., Hughes J.M., et al. RAGE: a new frontier in chronic airways disease. Br J Pharmacol 2012, 167:1161-1176.
298. Vij N. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential. Expert Opin Drug Deliv 2011, 8:1105-1109.
299. Da Silva A.L., Santos R.S., Xisto D.G., Alonso Sdel V., Morales M.M., Rocco P.R. Nanoparticle-based therapy for respiratory diseases. An Acad Bras Ciencias 2013, 85:137-146.
300. Kenyon N.J., Bratt J.M., Lee J., Luo J., Franzi L.M., Zeki A.A., et al. Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation. PloS one 2013, 8:e77730.
301. John A.E., Lukacs N.W., Berlin A.A., Palecanda A., Bargatze R.F., Stoolman L.M., et al. Discovery of a potent nanoparticle P-selectin antagonist with anti-inflammatory effects in allergic airway disease. FASEB J - Off Publ Fed Am Soc Exp Biology 2003, 17:2296-2298.
302. Matsuo Y., Ishihara T., Ishizaki J., Miyamoto K., Higaki M., Yamashita N. Effect of betamethasone phosphate loaded polymeric nanoparticles on a murine asthma model. Cell Immunol 2009, 260:33-38.
303. Geiser M., Quaile O., Wenk A., Wigge C., Eigeldinger-Berthou S., Hirn S., et al. Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease. Part Fibre Toxicol 2013, 10:19.
304. Hussain S., Vanoirbeek J.A., Luyts K., De Vooght V., Verbeken E., Thomassen L.C., et al. Lung exposure to nanoparticles modulates an asthmatic response in a mouse model. Eur Respir J Off J Eur Soc Clin Respir Physiol 2011, 37:299-309.
305. Gwinn M.R., Vallyathan V. Nanoparticles: health effects-pros and cons. Environ health perspect 2006, 114:1818-1825.