Advanced Microengineered Lung Models for Translational Drug Discovery

SLAS Discovery

Volumn 23, Issue 8, 2018, Pages 777-789

  Niemeyer, Brian F ^a   Zhao, Peng ^a   Tuder, Rubin M ^a   Benam, Kambez H ^a,b  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b The University of Colorado Denver   (United States)

Author keywords

biomarkers; breathing smoking human lung on a chip; drug development; lungs; small airway on a chip; translational respiratory medicine

Indexed keywords

BIOLOGICAL MARKER; CYTOKINE; HEME OXYGENASE 1; INTERLEUKIN 6; INTERLEUKIN 8; INTERSTITIAL COLLAGENASE; PROLINE RICH PROTEIN; TOLL LIKE RECEPTOR 8;

CELL CULTURE TECHNIQUE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CYSTIC FIBROSIS; DRUG DESIGN; DRUG SCREENING; EXTRACELLULAR MATRIX; FIBROSING ALVEOLITIS; GENE EXPRESSION; HUMAN; HYPERTENSION; INFLAMMATION; LUNG ALVEOLUS; LUNG DISEASE; LUNG EDEMA; LUNG MODEL; NON SMALL CELL LUNG CANCER; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; RISK FACTOR; SMALL AIRWAY DISEASE; SMOKING; UPREGULATION; ANIMAL; DEVICES; DRUG DEVELOPMENT; DRUG EFFECT; LAB ON A CHIP; LUNG; PRECLINICAL STUDY; PROCEDURES; REPRODUCIBILITY; TISSUE CULTURE TECHNIQUE; TISSUE ENGINEERING; TRANSLATIONAL RESEARCH;

ANIMALS; BIOMARKERS; CELL CULTURE TECHNIQUES; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; LAB-ON-A-CHIP DEVICES; LUNG; LUNG DISEASES; REPRODUCIBILITY OF RESULTS; TISSUE CULTURE TECHNIQUES; TISSUE ENGINEERING; TRANSLATIONAL MEDICAL RESEARCH;

EID: 85052132475     PISSN: 24725552     EISSN: 24725560     Source Type: Journal    
DOI: 10.1177/2472555218760217     Document Type: Review

References (112)

1. Shih H. P., Zhang X., Aronov A. M., Drug Discovery Effectiveness from the Standpoint of Therapeutic Mechanisms and Indications. Nat. Rev. Drug Discov. 2017
2. US Food and Drug Administration. The Drug Development Process. 2015. https://www.fda.gov/forpatients/approvals/drugs/
3. Paul S. M., Mytelka D. S., Dunwiddie C. T.. How to Improve R&D Productivity: The Pharmaceutical Industry’s Grand Challenge. Nat. Rev. Drug Discov. 2010, 9 (3), 203–214
4. Hughes J. P., Rees S., Kalindjian S. B.. Principles of Early Drug Discovery. Br. J. Pharmacol. 2011, 162 (6), 1239–1249
5. DiMasi J. A., Grabowski H. G., Hansen R. W., Innovation in the Pharmaceutical Industry: New Estimates of R&D Costs. J. Health Econ. 2016, 47, 20–33
6. Mullard A., Parsing Clinical Success Rates. Nat. Rev. Drug Discov. 2016, 15 (7), 447
7. Arrowsmith J., Miller P., Trial Watch: Phase II and Phase III Attrition Rates 2011–2012. Nat. Rev. Drug Discov. 2013, 12 (8), 569
8. Imura Y., Yoshimura E., Sato K., Microcirculation System with a Dialysis Part for Bioassays Evaluating Anticancer Activity and Retention. Anal. Chem. 2013, 85 (3), 1683–1688
9. Seok J., Warren H. S., Cuenca A. G.. Genomic Responses in Mouse Models Poorly Mimic Human Inflammatory Diseases. Proc. Natl. Acad. Sci. USA 2013, 110 (9), 3507–3512
10. Henderson V. C., Kimmelman J., Fergusson D.. Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for in Vivo Animal Experiments. PLoS Med. 2013, 10 (7), e1001489
11. Festing S., Wilkinson R., The Ethics of Animal Research: Talking Point on the Use of Animals in Scientific Research. EMBO Rep. 2007, 8 (6), 526–530
12. Bhatia S. N., Ingber D. E., Microfluidic Organs-on-Chips. Nat. Biotechnol. 2014, 32 (8), 760–772
13. Huh D., Hamilton G. A., Ingber D. E., From 3D Cell Culture to Organs-on-Chips. Trends Cell Biol. 2011, 21 (12), 745–754
14. Barnes P. J., Bonini S., Seeger W.. Barriers to New Drug Development in Respiratory Disease. Eur. Respir. J. 2015, 45 (5), 1197–1207
15. Ferkol T., Schraufnagel D., The Global Burden of Respiratory Disease. Ann. Amer. Thorac. Soc. 2014, 11 (3), 404–406
16. World Health Organization. The Top 10 Causes of Death. 2017. http://www.who.int/mediacentre/factsheets/fs310/en/
17. Martinez F. D., Early-Life Origins of Chronic Obstructive Pulmonary Disease. New Engl. J. Med. 2016, 375 (9), 871–878
18. COPD Foundation. COPD Statistics across America. 2017. https://www.copdfoundation.org/what-is-copd/copd-facts/statistics.aspx
19. Mannino D. M., Higuchi K., Yu T. C.. Economic Burden of COPD in the Presence of Comorbidities. Chest 2015, 148 (1), 138–150
20. Al-Tawfiq J. A., Zumla A., Gautret P.. Surveillance for Emerging Respiratory Viruses. Lancet Infect. Dis. 2014, 14 (10), 992–1000
21. Stenmark K. R., Meyrick B., Galie N.. Animal Models of Pulmonary Arterial Hypertension: The Hope for Etiological Discovery and Pharmacological Cure. Am. J. Physiol. Lung Cell Mol. Physiol. 2009, 297 (6), L1013–L1032
22. Canning B. J., Wright J. L., Animal Models of Asthma and Chronic Obstructive Pulmonary Disease. Pulm. Pharmacol. Ther. 2008, 21 (5), 695
23. Wright J. L., Cosio M., Churg A., Animal Models of Chronic Obstructive Pulmonary Disease. Am. J. Physiol. Lung Cell Mol. Physiol. 2008, 295 (1), L1–L15
24. Hyde D. M., Hamid Q., Irvin C. G., Anatomy, Pathology, and Physiology of the Tracheobronchial Tree: Emphasis on the Distal Airways. J. Allergy Clin. Immunol. 2009, 124 (6 Suppl.), S72–S77
25. Kolaczkowska E., Kubes P., Neutrophil Recruitment and Function in Health and Inflammation. Nature Rev. Immunol. 2013, 13 (3), 159–175
26. Benam K. H., Villenave R., Lucchesi C.. Small Airway-on-a-Chip Enables Analysis of Human Lung Inflammation and Drug Responses in Vitro. Nat. Methods 2016, 13 (2), 151–157
27. Hecht S. S., Carcinogenicity Studies of Inhaled Cigarette Smoke in Laboratory Animals: Old and New. Carcinogenesis 2005, 26 (9), 1488–1492
28. Benam K. H., Novak R., Nawroth J.. Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using a Microengineered Breathing Lung Chip. Cell Syst. 2016, 3 (5), 456–466 e4
29. Huh D., Matthews B. D., Mammoto A.. Reconstituting Organ-Level Lung Functions on a Chip. Science 2010, 328 (5986), 1662–1668
30. Fang Y., Eglen R. M., Three-Dimensional Cell Cultures in Drug Discovery and Development. SLAS Discov. 2017, 22 (5), 456–472
31. Amann A., Zwierzina M., Gamerith G.. Development of an Innovative 3D Cell Culture System to Study Tumour–Stroma Interactions in Non-Small Cell Lung Cancer Cells. PLoS One 2014, 9 (3), e92511
32. Chimenti I., Pagano F., Angelini F.. Human Lung Spheroids as in Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties. Stem Cells Translat. Med. 2017, 6 (3), 767–777
33. Barkauskas C. E., Chung M. I., Fioret B.. Lung Organoids: Current Uses and Future Promise. Development 2017, 144 (6), 986–997
34. Lee J. H., Bhang D. H., Beede A.. Lung Stem Cell Differentiation in Mice Directed by Endothelial Cells via a BMP4-NFATc1-Thrombospondin-1 Axis. Cell 2014, 156 (3), 440–455
35. Dye B. R., Hill D. R., Ferguson M. A.. In Vitro Generation of Human Pluripotent Stem Cell Derived Lung Organoids. Elife 2015, 4
36. Nikolic M. Z., Caritg O., Jeng Q.. Human Embryonic Lung Epithelial Tips Are Multipotent Progenitors That Can Be Expanded in Vitro as Long-Term Self-Renewing Organoids. Elife 2017, 6
37. Nadkarni R. R., Abed S., Draper J. S., Organoids as a Model System for Studying Human Lung Development and Disease. Biochem. Biophys. Res. Commun. 2016, 473 (3), 675–682
38. Nikolic M. Z., Rawlins E. L., Lung Organoids and Their Use To Study Cell-Cell Interaction. Curr. Pathobiol. Rep. 2017, 5 (2), 223–231
39. Pouliot R. A., Link P. A., Mikhaiel N. S.. Development and Characterization of a Naturally Derived Lung Extracellular Matrix Hydrogel. J. Biomed. Mater. Res. A 2016, 104 (8), 1922–1935
40. Ingenito E. P., Sen E., Tsai L. W.. Design and Testing of Biological Scaffolds for Delivering Reparative Cells to Target Sites in the Lung. J. Tissue Eng. Regen. Med. 2010, 4 (4), 259–272
41. El-Sherbiny I. M., Yacoub M. H., Hydrogel Scaffolds for Tissue Engineering: Progress and Challenges. Glob. Cardiol. Sci. Pract. 2013, 2013 (3), 316–342
42. Naahidi S., Jafari M., Logan M.. Biocompatibility of Hydrogel-Based Scaffolds for Tissue Engineering Applications. Biotechnol. Adv. 2017, 35 (5), 530–544
43. Hoare T. R., Kohane D. S., Hydrogels in Drug Delivery: Progress and Challenges. Polymer 2008, 49 (8), 1993–2007
44. Smithmyer M. E., Sawicki L. A., Kloxin A. M., Hydrogel Scaffolds as in Vitro Models to Study Fibroblast Activation in Wound Healing and Disease. Biomater. Sci. 2014, 2 (5), 634–650
45. Petrini P., Fare S., Piva A.. Design, Synthesis and Properties of Polyurethane Hydrogels for Tissue Engineering. J. Mater. Sci. Mater. Med. 2003, 14 (8), 683–686
46. Horvath L., Umehara Y., Jud C.. Engineering an in Vitro Air-Blood Barrier by 3D Bioprinting. Sci. Rep. 2015, 5, 7974
47. Kolesky D. B., Homan K. A., Skylar-Scott M. A.. Three-Dimensional Bioprinting of Thick Vascularized Tissues. Proc. Natl. Acad. Sci. USA 2016, 113 (12), 3179–3184
48. Wust S., Muller R., Hofmann S., Controlled Positioning of Cells in Biomaterials: Approaches towards 3D Tissue Printing. J. Funct. Biomater. 2011, 2 (3), 119–154
49. Gao G., Huang Y., Schilling A. F.. Organ Bioprinting: Are We There Yet? Adv. Healthcare Mater. 2017, 6 (1)
50. Kolesky D. B., Truby R. L., Gladman A. S.. 3D Bioprinting of Vascularized, Heterogeneous Cell-Laden Tissue Constructs. Adv. Mater. 2014, 26 (19), 3124–3130
51. Murphy S. V., Atala A., 3D Bioprinting of Tissues and Organs. Nat. Biotechnol. 2014, 32 (8), 773–785
52. Pati F., Jang J., Ha D. H.. Printing Three-Dimensional Tissue Analogues with Decellularized Extracellular Matrix Bioink. Nat. Commun. 2014, 5, 3935
53. Munaz A., Vadivelu R. K., St. John J.. Three-Dimensional Printing of Biological Matters. J. Sci. Adv. Mater. Dev. 2016, 1 (1), 1–17
54. Morin J. P., Baste J. M., Gay A.. Precision Cut Lung Slices as an Efficient Tool for in Vitro Lung Physio-Pharmacotoxicology Studies. Xenobiotica 2013, 43 (1), 63–72
55. Sanderson M. J., Exploring Lung Physiology in Health and Disease with Lung Slices. Pulm. Pharmacol. Ther. 2011, 24 (5), 452–465
56. Esch M. B., Sung J. H., Yang J.. On Chip Porous Polymer Membranes for Integration of Gastrointestinal Tract Epithelium with Microfluidic “Body-on-a-Chip” Devices. Biomed. Microdev. 2012, 14 (5), 895–906
57. Neuhaus V., Schaudien D., Golovina T.. Assessment of Long-Term Cultivated Human Precision-Cut Lung Slices as an ex Vivo System for Evaluation of Chronic Cytotoxicity and Functionality. J. Occup. Med. Toxicol. 2017, 12, 13
58. Henjakovic M., Sewald K., Switalla S.. Ex Vivo Testing of Immune Responses in Precision-Cut Lung Slices. Toxicol. Appl. Pharmacol. 2008, 231 (1), 68–76
59. Benam K. H., Dauth S., Hassell B.. Engineered in Vitro Disease Models. Annu. Rev. Pathol. 2015, 10, 195–262
60. Selimovic S., Dokmeci M. R., Khademhosseini A., Organs-on-a-Chip for Drug Discovery. Curr. Opin. Pharmacol. 2013, 13 (5), 829–333
61. Lee P. J., Hung P. J., Lee L. P., An Artificial Liver Sinusoid with a Microfluidic Endothelial-Like Barrier for Primary Hepatocyte Culture. Biotechnol. Bioengin. 2007, 97 (5), 1340–1346
62. Viravaidya K., Shuler M. L., Incorporation of 3T3-L1 Cells to Mimic Bioaccumulation in a Microscale Cell Culture Analog Device for Toxicity Studies. Biotechnol. Prog. 2004, 20 (2), 590–597
63. Sin A., Chin K. C., Jamil M. F.. The Design and Fabrication of Three-Chamber Microscale Cell Culture Analog Devices with Integrated Dissolved Oxygen Sensors. Biotechnol. Prog. 2004, 20 (1), 338–345
64. Chao P., Maguire T., Novik E.. Evaluation of a Microfluidic Based Cell Culture Platform with Primary Human Hepatocytes for the Prediction of Hepatic Clearance in Human. Biochem. Pharmacol. 2009, 78 (6), 625–632
65. Legendre A., Baudoin R., Alberto G.. Metabolic Characterization of Primary Rat Hepatocytes Cultivated in Parallel Microfluidic Biochips. J. Pharm. Sci. 2013, 102 (9), 3264–3276
66. Cheng S., Prot J. M., Leclerc E.. Zonation Related Function and Ubiquitination Regulation in Human Hepatocellular Carcinoma Cells in Dynamic vs. Static Culture Conditions. BMC Genomics 2012, 13, 54
67. Novik E., Maguire T. J., Chao P.. A Microfluidic Hepatic Coculture Platform for Cell-Based Drug Metabolism Studies. Biochem. Pharmacol. 2010, 79 (7), 1036–1044
68. Jang K. J., Suh K. Y., A Multi-Layer Microfluidic Device for Efficient Culture and Analysis of Renal Tubular Cells. Lab on a Chip 2010, 10 (1), 36–42
69. Snouber L. C., Letourneur F., Chafey P.. Analysis of Transcriptomic and Proteomic Profiles Demonstrates Improved Madin-Darby Canine Kidney Cell Function in a Renal Microfluidic Biochip. Biotechnol. Prog. 2012, 28 (2), 474–484
70. Jang K. J., Mehr A. P., Hamilton G. A.. Human Kidney Proximal Tubule-on-a-Chip for Drug Transport and Nephrotoxicity Assessment. Integr. Biol. (Camb.) 2013, 5 (9), 1119–1129
71. Kim H. J., Huh D., Hamilton G.. Human Gut-on-a-Chip Inhabited by Microbial Flora That Experiences Intestinal Peristalsis-Like Motions and Flow. Lab on a Chip 2012, 12 (12), 2165–2174
72. Kim H. J., Ingber D. E., Gut-on-a-Chip Microenvironment Induces Human Intestinal Cells to Undergo Villus Differentiation. Integr. Biol. (Camb.) 2013, 5 (9), 1130–1140
73. Zhang Y., Gazit Z., Pelled G.. Patterning Osteogenesis by Inducible Gene Expression in Microfluidic Culture Systems. Integr. Biol. (Camb.) 2011, 3 (1), 39–47
74. Park S. H., Sim W. Y., Min B. H.. Chip-Based Comparison of the Osteogenesis of Human Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells under Mechanical Stimulation. PLoS One 2012, 7 (9), e46689
75. Zhang W., Lee W. Y., Siegel D. S.. Patient-Specific 3D Microfluidic Tissue Model for Multiple Myeloma. Tissue Engin. Part C Methods 2014, 20 (8), 663–670
76. Booth R., Kim H., Characterization of a Microfluidic in Vitro Model of the Blood-Brain Barrier (muBBB). Lab on a Chip 2012, 12 (10), 1784–1792
77. Huh D., Leslie D. C., Matthews B. D.. A Human Disease Model of Drug Toxicity-Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice. Sci. Transl. Med. 2012, 4 (159), 159ra147
78. Liu M. C., Shih H. C., Wu J. G.. Electrofluidic Pressure Sensor Embedded Microfluidic Device: A Study of Endothelial Cells under Hydrostatic Pressure and Shear Stress Combinations. Lab on a Chip 2013, 13 (9), 1743–1753
79. van der Meer A. D., Orlova V. V., ten Dijke P.. Three-Dimensional Co-Cultures of Human Endothelial Cells and Embryonic Stem Cell-Derived Pericytes inside a Microfluidic Device. Lab on a Chip 2013, 13 (18), 3562–3568
80. Grosberg A., Nesmith A. P., Goss J. A.. Muscle on a Chip: In Vitro Contractility Assays for Smooth and Striated Muscle. J. Pharmacol. Toxicol. Methods 2012, 65 (3), 126–135
81. O’Neill A. T., Monteiro-Riviere N. A., Walker G. M., Characterization of Microfluidic Human Epidermal Keratinocyte Culture. Cytotechnology 2008, 56 (3), 197–207
82. Sobue K., Yamamoto N., Yoneda K.. Induction of Blood-Brain Barrier Properties in Immortalized Bovine Brain Endothelial Cells by Astrocytic Factors. Neurosci. Res. 1999, 35 (2), 155–164
83. Shayan G., Choi Y. S., Shusta E. V.. Murine in Vitro Model of the Blood-Brain Barrier for Evaluating Drug Transport. European J. Pharma. Sci. 2011, 42 (1–2), 148–155
84. Achyuta A. K., Conway A. J., Crouse R. B.. A Modular Approach to Create a Neurovascular Unit-on-a-Chip. Lab on a Chip 2013, 13 (4), 542–553
85. Griep L. M., Wolbers F., de Wagenaar B.. BBB on Chip: Microfluidic Platform to Mechanically and Biochemically Modulate Blood-Brain Barrier Function. Biomed. Microdev. 2013, 15 (1), 145–150
86. Torisawa Y. S., Spina C. S., Mammoto T.. Bone Marrow-on-a-Chip Replicates Hematopoietic Niche Physiology in Vitro. Nat. Methods 2014, 11 (6), 663–669
87. Ziegler L., Grigoryan S., Yang I. H.. Efficient Generation of Schwann Cells from Human Embryonic Stem Cell-Derived Neurospheres. Stem Cell Rev. 2011, 7 (2), 394–403
88. Park H. S., Liu S., McDonald J.. Neuromuscular Junction in a Microfluidic Device. Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2013, 2013, 2833–2835
89. Shi M., Majumdar D., Gao Y.. Glia Co-Culture with Neurons in Microfluidic Platforms Promotes the Formation and Stabilization of Synaptic Contacts. Lab on a Chip 2013, 13 (15), 3008–3021
90. Tsantoulas C., Farmer C., Machado P.. Probing Functional Properties of Nociceptive Axons Using a Microfluidic Culture System. PLoS One 2013, 8 (11), e80722
91. Xiao R. R., Zeng W. J., Li Y. T.. Simultaneous Generation of Gradients with Gradually Changed Slope in a Microfluidic Device for Quantifying Axon Response. Anal. Chem. 2013, 85 (16), 7842–7850
92. Musah S., Mammoto A., Ferrante T. C.. Mature Induced-Pluripotent-Stem-Cell-Derived Human Podocytes Reconstitute Kidney Glomerular-Capillary-Wall Function on a Chip. Nat. Biomed. Eng. 2017, 1
93. Hogg J. C., Chu F., Utokaparch S.. The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease. New Engl. J. Med. 2004, 350 (26), 2645–2653
94. Burgel P. R., de Blic J., Chanez P.. Update on the Roles of Distal Airways in Asthma. Eur. Respir. Rev. 2009, 18 (112), 80–95
95. Tiddens H. A., Donaldson S. H., Rosenfeld M.. Cystic Fibrosis Lung Disease Starts in the Small Airways: Can We Treat It More Effectively? Pediatric Pulmonol. 2010, 45 (2), 107–117
96. Benam K. H., Mazur M., Choe Y.. Human Lung Small Airway-on-a-Chip Protocol. Methods Mol. Biol. 2017, 1612, 345–365
97. Tashkin D. P., Murray R. P., Smoking Cessation in Chronic Obstructive Pulmonary Disease. Resp. Med. 2009, 103 (7), 963–974
98. Benam K. H., Ingber D. E., Commendation for Exposing Key Advantage of Organ Chip Approach. Cell Syst. 2016, 3 (5), 411
99. Benam K. H., Konigshoff M., Eickelberg O., Breaking the in Vitro Barrier in Respiratory Medicine: Engineered Microphysiological Systems for COPD and Beyond. Am. J. Respir. Crit. Care Med. [Online]. doi:10.1164/rccm.201709-1795PP. https://www.ncbi.nlm.nih.gov/pubmed/29262260
100. Bertram K. M., Baglole C. J., Phipps R. P.. Molecular Regulation of Cigarette Smoke Induced-Oxidative Stress in Human Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration. Amer. J. Physiol. Cell Physiol. 2009, 297 (5), C1200–C1210
101. Barkal L. J., Procknow C. L., Alvarez-Garcia Y. R.. Microbial Volatile Communication in Human Organotypic Lung Models. Nat. Commun. 2017, 8 (1), 1770
102. Deslee G., Dury S., Perotin J. M.. Bronchial Epithelial Spheroids: An Alternative Culture Model to Investigate Epithelium Inflammation-Mediated COPD. Respir. Res. 2007, 8, 86
103. Bafadhel M., McKenna S., Terry S.. Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Identification of Biologic Clusters and Their Biomarkers. Am. J. Respir. Crit. Care Med. 2011, 184 (6), 662–671
104. Quint J. K., Donaldson G. C., Goldring J. J.. Serum IP-10 as a Biomarker of Human Rhinovirus Infection at Exacerbation of COPD. Chest 2010, 137 (4), 812–822
105. Dickens J. A., Miller B. E., Edwards L. D.. COPD Association and Repeatability of Blood Biomarkers in the ECLIPSE Cohort. Respir. Res. 2011, 12, 146
106. Thodeti C. K., Matthews B., Ravi A.. TRPV4 Channels Mediate Cyclic Strain-Induced Endothelial Cell Reorientation through Integrin-to-Integrin Signaling. Circ. Res. 2009, 104 (9), 1123–1130
107. Thorneloe K. S., Cheung M., Bao W.. An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure. Sci. Transl. Med. 2012, 4 (159), 159ra148
108. Bush A., Hedlin G., Carlsen K. H.. Severe Childhood Asthma: A Common International Approach? Lancet 2008, 372 (9643), 1019–1021
109. Wedzicha J. A., Role of Viruses in Exacerbations of Chronic Obstructive Pulmonary Disease. Proc. Am. Thorac. Soc. 2004, 1 (2), 115–120
110. Di Stefano A., Capelli A., Lusuardi M.. Severity of Airflow Limitation Is Associated with Severity of Airway Inflammation in Smokers. Am. J. Respir. Crit. Care Med. 1998, 158 (4), 1277–1285
111. Jain A., Barrile R., van der Meer A. D.. Primary Human Lung Alveolus-on-a-Chip Model of Intravascular Thrombosis for Assessment of Therapeutics. Clin. Pharmacol. Ther. 2017
112. Schork N. J., Personalized Medicine: Time for One-Person Trials. Nature 2015, 520 (7549), 609–611