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Training Grant-
Biology of Aging

Keith Meyer

Keith C. Meyer

M.D., University of Wisconsin-Madison
Professor, Department of Medicine

Respiratory Function and Advancing Age

Lung function gradually deteriorates with advancing age and appears to be a natural process that occurs even in the absence of exposure to tobacco or other substances capable of promoting lung irritation and inflammation. Some of these changes are similar to those associated with emphysema, although to a milder degree. My research has focused on the immune system in the lung and what factors may contribute to age-associated decline in lung function and increased susceptibility to lung infection. I have found that the quantity and profile of immune cells and proteins retrieved from the lungs of older, seemingly healthy individuals differ from that of younger, healthy subjects. Older individuals have increased numbers of inflammatory cells and proteins in their lung secretions compared to younger individuals, and I have postulated that "low-grade inflammation" in older individuals may play a role in the gradual decline in lung function that occurs in association with advancing age.

A decline in the production of a substance called vascular endothelial growth factor (VEGF), a protein that appears to be important for maintaining the rich network of small blood vessels in the lung, has been found in patients who have emphysema. I have found that a decline in VEGF concentrations in lung secretions is associated with advancing age, suggesting that altered production of VEGF may be linked to the milder, emphysema-like changes that occur in the aging lung. Investigations such as these may provide insights that allow pharmacologic interventions to be developed that prevent or blunt age-associated deterioration in lung structure and function as well as bolster resistance to respiratory tract infections in the elderly individual.

I am also interested in clinical aspects of the association of advancing age and susceptibility to lung infection or other disorders such as idiopathic pulmonary fibrosis. Special consideration needs to be given to the diagnosis and treatment of infectious and non-infectious pulmonary disorders when they occur in an elderly individual.

Currently, I am the guest editor for an issue in Seminars in Respiratory and Critical Care Medicine that deals with various aspects of aging and how the lungs change/are affected with advancing age ("Impact of Aging on the Lung").

Representative Publications
Haynes, L. D., Julliard, W., Mezrich, J., Leverson, G., Meyer, K. C., & Burlingham, W. J (2018). Specific donor HLA-DR types correlate with altered susceptibility to development of chronic lung allograft dysfunction. Transplantation. Advance online publication.
View publication via DOI: DOI:10.1097/tp.0000000000002107

Diamond, J. M., Cantu, E., Porteous, M. K., Suzuki, Y., Meyer, K. C., Lederer, D. J., . . . Christie, J. D. (2017). Peripheral blood gene expression changes associated with primary graft dysfunction after lung transplantation. American Journal of Transplantation, 17(7), 1770-1777.
View publication via DOI: DOI:10.1111/ajt.14209

Meyer, K. C. (2017). Great expectations for simtuzumab in IPF fall short. Lancet Respiratory Medicine, 5(1), 2-3.
View publication via DOI: DOI:10.1016/s2213-2600(16)30420-9

Meyer, K. C. (2017). Pulmonary fibrosis, part I: Epidemiology, pathogenesis, and diagnosis. Expert Review of Respiratory Medicine, 11(5), 343-359.
View publication via DOI: DOI:10.1080/17476348.2017.1312346

Meyer, K. C. (2017). Pulmonary fibrosis, part II: State-of-the-art patient management. Expert Review of Respiratory Medicine, 11(5), 361-376.
View publication via DOI: DOI:10.1080/17476348.2017.1312347

Meyer, K. C., & Decker, C. A. (2017). Role of pirfenidone in the management of pulmonary fibrosis. Therapeutics and Clinical Risk Management, 13, 427-437.
View publication via DOI: DOI:10.2147/tcrm.s81141

De Oliveira, N. C., Julliard, W., Osaki, S., Maloney, J. D., Cornwell, R. D., Sonetti, D. A., & Meyer, K. C. (2016). Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases, 33(3), 235-241.

Julliard, W. A., Meyer, K. C., De Oliveira, N. C., Osaki, S., Cornwell, R. C., Sonetti, D. A., & Maloney, J. D. (2016). The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation. Thorax, 71(5), 478-480.
View publication via DOI: DOI:10.1136/thoraxjnl-2015-207354

Lushaj, E., Julliard, W., Akhter, S., Leverson, G., Maloney, J. D., Cornwell, R. D., ... Meyer, K. C., ... DeOliveira, N. (2016). Timing and frequency of unplanned readmissions after lung transplantation impact long-term survival. Annals of Thoracic Surgery, 102(2), 378-384.
View publication via DOI: DOI:10.1016/j.athoracsur.2016.02.083

Welsh, C. H., Wang, T. S., Lyu, D. M., Orr, J., Meyer, K. C., Glanville, A. R., Verleden, G. M., Wilson, K. C., Thomson, C. C., & The American Thoracic Society Implementation Task Force. (2015). An international ISHLT/ATS/ERS clinical practice guideline: Summary for clinicians. Bronchiolitis obliterans syndrome complicating lung transplantation. Annals of the American Thoracic Society, 12(1), 118-119.
View publication via DOI: DOI:10.1513/AnnalsATS.201410-471CME

Meyer, K. C., Danoff, S. K., Lancaster, L. H., & Nathan, S. D. (2015). Management of idiopathic pulmonary fibrosis in the elderly patient: Addressing key questions. Chest, 148(1), 242-252.
View publication via DOI: DOI:10.1378/chest.14-2475

Cullinane, A. R., Yeager, C., Dorward, H., Carmona-Rivera, C., Wu, H. P., Moss, J., O'Brien, K. J., Nathan, S. D., Meyer, K. C., Rosas, I. O., Helip-Wooley, A., Huizing, M., Gahl, W. A., & Gochuico, B. R. (2014). Dysregulation of galectin-3. Implications for hermansky-pudlak syndrome pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, 50(3), 605-613.
View publication via DOI: DOI:10.1165/rcmb.2013-0025OC

Meyer, K. C. (2014). Diagnosis and management of interstitial lung disease. Translational Respiratory Medicine, 2, 4.
View publication via DOI: DOI:10.1186/2213-0802-2-4

Meyer, K. C. (2014). Immunosuppressive agents and interstitial lung disease: What are the risks? Expert Review of Respiratory Medicine, 8(3), 263-266.
View publication via DOI: DOI:10.1586/17476348.2014.880054

Meyer, K. C. (2014). The clinical utility of bronchoalveolar lavage in interstitial lung disease - is it really useful? Expert Review of Respiratory Medicine, 8(2), 133-135.
View publication via DOI: DOI:10.1586/17476348.2014.879827

Meyer, K. C., Raghu, G., Verleden, G. M., Corris, P. A., Aurora, P., Wilson, K. C., Brozek, J., & Glanville, A. R (2014). An international ISHLT/ATS/ERS clinical practice guideline: Diagnosis and management of bronchiolitis obliterans syndrome. The European Respiratory Journal, 44(6), 1479-1503.
View publication via DOI: DOI:10.1183/09031936.00107514

Nathan, S. D., & Meyer, K. C. (2014). Ipf clinical trial design and endpoints. Current Opinion in Pulmonary Medicine, 20(5), 463-471.
View publication via DOI: DOI:10.1097/mcp.0000000000000091

Schmidt, A., Belaaouaj, A., Bissinger, R., Koller, G., Malleret, L., D'Orazio, C., Facchinelli, M., Schulte-Hubbert, B., Molinaro, A., Holst, O., Hammermann, J., Schniederjans, M., Meyer, K. C., Damkiaer, S., Piacentini, G., Assael, B., Bruce, K., Haussle (2014). Neutrophil elastase-mediated increase in airway temperature during inflammation. Journal of Cystic Fibrosis, 13(6), 623-631.
View publication via DOI: DOI:10.1016/j.jcf.2014.03.004

Verleden, G. M., Raghu, G., Meyer, K. C., Glanville, A. R., & Corris, P. (2014). A new classification system for chronic lung allograft dysfunction. Journal of Heart and Lung Transplantation, 33(2), 127-133.
View publication via DOI: DOI:10.1016/j.healun.2013.10.022

Egressy, K., Jansen, M., & Meyer, K. C. (2013). Recurrent Clostridium difficile colitis in cystic fibrosis: An emerging problem. Journal of Cystic Fibrosis, 12(1), 92-96.
View publication via DOI: DOI:10.1016/j.jcf.2012.05.007

Nguyen, W., & Meyer, K. C. (2013). Surgical lung biopsy for the diagnosis of interstitial lung disease: A review of the literature and recommendations for optimizing safety and efficacy. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases, 30(1), 3-16.

Colman, R. E., Curtis, J. R., Nelson, J. E., Efferen, L., Hadjiliadis, D., Levine, D. J., Meyer, K. C. . . . Singer, L. G. (2013). Barriers to optimal palliative care of lung transplant candidates. Chest, 143(3), 736-743.
View publication via DOI: DOI:10.1378/chest.12-0830

Denlinger, L. C., Kelly, E. A., Dodge, A. M., McCartney, J. G., Meyer, K. C., Cornwell, R. D., . . . Jarjour, N. N. (2013). Safety of and cellular response to segmental bronchoprovocation in allergic asthma. PLoS One, 8(1), e51963.
View publication via DOI: DOI:10.1371/journal.pone.0051963

Meyer, K. C. (2013). Lung transplantation. F1000Prime Reports, 5, 16.
View publication via DOI: DOI:10.12703/p5-16

Meyer, K. C., & Raghu, G. (2013). Reply: The clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. American Journal of Respiratory and Critical Care Medicine, 187(7), 777-778.
View publication via DOI: DOI:10.1164/ajrccm.187.7.777a

Cantu, E., Lederer, D. J., Meyer, K. C., Milewski, K., Suzuki, Y., Shah, R. J., . . . Christie, J. D. (2013). Gene set enrichment analysis identifies key innate immune pathways in primary graft dysfunction after lung transplantation. American Journal of Transplantation, 13(7), 1898-1904.
View publication via DOI: DOI:10.1111/ajt.12283

Meyer, K. C., & Raghu, G. (2013). Reply: Performing bronchoalveolar lavage as per the ATS Guidelines 2012. American Journal of Respiratory and Critical Care Medicine, 188(1), 113-114.
View publication via DOI: DOI:10.1164/rccm.201301-0163LE

Worlitzsch, D., Meyer, K. C., & Doring, G. (2013). Lactate levels in airways of patients with cystic fibrosis and idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 188(1), 111-111.
View publication via DOI: DOI:10.1164/rccm.201211-2042LE

De Oliveira, N.C., Osaki, S., Maloney, J.D., Cornwell, R.D., & Meyer, K.C. (2012). Lung transplant for interstitial lung disease: outcomes before and after implementation of the UNOS lung allocation scoring system. European Journal of Cardio-Thoracic Surgery, 41(3), 680-5.
View publication via DOI: DOI:10.1093/ejcts/ezr079

De Oliveira, N.C., Osaki, S., Maloney, J.D., Cornwell, R.D., & Meyer, K.C. (2012). Lung transplant for interstitial lung disease: outcomes for single versus bilateral lung transplantation. Interactive Cardiovascular and Thoracic Surgery, 14(3), 263-7.
View publication via DOI: DOI:10.1093/icvts/ivr085

Raghu, G. & Meyer, K.C. (2012). Silent gastro-oesophageal reflux and microaspiration in IPF: mounting evidence for anti-reflux therapy? European Respiratory Journal, 39(2), 242-5.
View publication via DOI: DOI:10.1183/09031936.00211311

Meyer, K.C., Raghu, G., Baughman, R.P., Brown, K.K., Costabel, U., du Bois, R.M., ... Wood, B. (2012). An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. American Journal of Respiratory and Critical Care Medicine,, 185(9), 1004-1014.
View publication via DOI: DOI:10.1164/rccm.201202-0320ST

Tsao, F. H., Culver, B. J., Pierre, J. F., Shanmuganayagam, D., Patten, C. C., Jr., & Meyer, K. C. (2012). Effect of prophylactic supplementation with grape polyphenolics on endotoxin-induced serum secretory phospholipase A2 activity in rats. Comparative Medicine, 62(4), 271-278.

Meyer, K. C. (2012). Management of interstitial lung disease in elderly patients. Current Opinion in Pulmonary Medicine, 18(5), 483-492.
View publication via DOI: DOI:10.1097/MCP.0b013e3283541337

Collard, H. R., Morris, A., Daley, C. L., Humbert, M., & Meyer, K. C. (2012). Clinical year in review IV: HIV, mycobacterial disease, pulmonary hypertension, and interstitial lung disease. Proceedings of the American Thoracic Society, 9(4), 204-209.
View publication via DOI: DOI:10.1513/pats.201207-035TT

Meyer, K. C. (2012). Bronchiolitis obliterans syndrome. Current Respiratory Care Reports, 1(3), 147-156.
View publication via DOI: DOI:10.1007/s13665-012-0020-2

Tsao, F., Xiang, Z., Abbasi, A., & Meyer, K. C. (2012). Neutrophil necrosis and annexin 1 degradation associated with airway inflammation in lung transplant recipients with cystic fibrosis. BMC Pulmonary Medicine, 12(1), 1-10.
View publication via DOI: DOI:10.1186/1471-2466-12-44

Meyer, K. C., & Bierach, J. (2012). Immunosuppressive therapy for autoimmune lung diseases. Immunology and Allergy Clinics of North America, 32(4), 633-669.
View publication via DOI: DOI:10.1016/j.iac.2012.07.001

Baughman, R. P., Meyer, K. C., Nathanson, I., Angel, L., Bhorade, S. M., Chan, K. M., . . . Hayney, M. S., . . . Whelan, T. (2012). Executive summary: Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients: American college of chest physicians evidence-based clinical practice guidelines. Chest, 142(5), 1284-1288.
View publication via DOI: DOI:10.1378/chest.12-1075

Meyer, K.C. (2011). Interstitial lung disease in the elderly: pathogenesis, diagnosis and management. Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of World Association of Sarcoidosis and Other Granulomatous Disorders, 28(1), 3-17.

Meyer, K.C. (2011). The natural history and diagnosis of idiopathic pulmonary fibrosis: Are we all on the same page? Chest Journal, 140(1), 3-4.
View publication via DOI: DOI:10.1378/chest.11-0401

Meyer, K.C. & Raghu, G. (2011). Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful? European Resipratory Journal, 38, 761-769.
View publication via DOI: DOI:10.1183/09031936.00069509

Meyer, K.C., Francois, M.L., Thomas, H.K., Radford, K.L., Hawes, D.S., Mack, T.L., ... De Oliveira, N.C. (2011). Colon cancer in lung transplant recipients with CF: increased risk and results of screening. Journal of Cystic Fibrosis, 10(5), 366-369.
View publication via DOI: DOI:10.1016/j.jcf.2011.05.003

De Oliveira, N,C., Osaki, S., Maloney, J.D., Meyer, K.C., Kohmoto, T., D'Alessandro, A.M., & Love, R.B. (2010). Lung transplantation with donation after cardiac death donors: Long-term follow-up in a single center. Journal of thoracic and Cardiovascular Surgery, 139(5), 1306-1315.
Click here to download this publication.
View publication via DOI: DOI:10.1016/j.jtcvs.2010.02.004

Hayes, D., & Meyer, K.C. (2010). Lung transplantation for advanced bronchiectasis. Seminars in Respiratory and Critical Care Medicine, 31(2), 123-138.
Click here to download this publication.
View publication via DOI: DOI:10.1055/s-0030-1249109

Osaki, S., Maloney, J.D., Meyer, K.C., Cornwell, R.D., Edwards, N.M., & De Oliveira, N.C. (2009). The impact of the lung allocation scoring system at the single national Veterans Affairs Hospital lung transplantation program. European Journal of Cardio-Thoracic Surgery, 36(3), 467-501.
View publication via DOI: DOI:10.1016/j.ejcts.2009.03.013

Bobadilla, J.L., Love, R.B., Jankowska-Gan, E., Xu, Q., Haynes, L.D., Braun, R.K., Hayney, M.S., del Rio, A., deOliveira, N., Meyer, K., et al. (2008). TH-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am. J. Respir. Crit. Care Med., 177, 660-668.
View publication via DOI: DOI:10.1164/rccm.200612-1901OC

Peikert, T., Daniels, C.E., Beebe, T.J., Meyer, K.C., & Ryu, J.H. (2008). Assessment of current practice in the diagnosis and therapy of idiopathic pulmonary fibrosis. Respir. Med., 102(9), 1342-8.
View publication via DOI: DOI:10.1016/j.rmed.2008.03.018

McCartney, J., & Meyer, K.C. (2008). Optimizing post-transplant outcomes in lung transplantation. Expert Rev. Resp. Med., 2, 183-199.

Polomis, D., Runo, J.R., & Meyer, K.C. (2008). Pulmonary hypertension in interstitial lung disease. Curr. Opin. Pulm. Med., 14(5), 462-9.

Halsey, K.D., Wald, A., Meyer, K.C., Torrealba, J.R., & Gaumnitz, E.A. (2008). Non-acidic Supraesophageal reflux associated with diffuse alveolar damage and allograft dysfunction after lung transplantation: A case report. J. Heart Lung Transplant., 27(5), 564-7.
View publication via DOI: DOI:10.1016/j.healun.2008.01.020

Osaki, S., Maloney, J.D., Meyer, K.C., Cornwell, R.D., Edwards, N.M., & De Oliveira, N.C. (2008). Redo lung transplantation for acute and chronic lung allograft failure: long-term follow-up in a single center. Eur. J. Cardiothorac. Surg., 34(6), 1191-7.
View publication via DOI: DOI:10.1016/j.ejcts.2008.07.052

Kim, R., & Meyer, K.C. (2008). Therapies for interstitial lung disease: Past, present and future. Therapeutic Advances in Respiratory Disease, 2(5), 319-338.
View publication via DOI: DOI:10.1177/1753465808096948

Burlingham, W.J., Love, R.B., Jankowska-Gan, E., Haynes, L.D., Xu, Q., Bobadilla, J.L., Meyer, K.C., Hayney, M.S., Braun, R.K., Greenspan, D.S., Gopalakrishnan, B., Yoshida, S., Brand, D.D., Smith, G.N., Jr., Cummings, O.W., Cai, J., & Wilkes, D.S. (2007). Col V specific, IL17- and monokine-dependent cellular immunity predisposes to obliterative bronchiolitis after lung transplantation. J. Clin. Invest., 117(11), 3498-3506.
View publication via DOI: DOI:10.1172/JCI28031

Meyer, K. (2007). Lung transplant and cystic fibrosis: Who and when? Harrison's Online.

Meyer, K. (2007). Bronchoalveolar lavage in the diagnosis and management of interstitial lung disease. Clin. Pulm. Med., 14, 148-156.
View publication via DOI: DOI:10.1097/01.cpm.0000263483.00652.07

Spahr, J.E., Love, R.B., Francois, M., Radford, K., & Meyer, K.C. (2007). Lung transplantation for cystic fibrosis: current concepts and one center's experience. J. Cyst. Fibros., 6(5), 334-50.
View publication via DOI: DOI:10.1016/j.jcf.2006.12.010

Hayes, D. Jr., & Meyer, K.C. (2007). Acute exacerbations of chronic bronchitis in elderly patients: pathogenesis, diagnosis and management. Drugs Aging, 24(7), 555-72.

Tsao, F.H.C., Shanmuganayagam, D., Zachman, D.K., Khosravi, M., Folts, J.D., & Meyer, K.C. (2007). A continuous fluorescence assay for the determination of calcium-dependent secretory phospholipase A2 activity in serum. Clinica Chimica Acta, 379, 119-126.
View publication via DOI: DOI:10.1016/j.cca.2006.12.023

Meyer, K.C. (2007). Bronchoalveolar lavage as a diagnostic tool. Semin. Respir. Crit. Care Med., 28(5), 546-60.

Meyer, K. (2007). Diagnosing idiopathic pulmonary fibrosis, part 1: Presentation and diagnosis. J. Respir. Dis., 28, 283-292.

Meyer, K. (2007). Idiopathic pulmonary fibrosis, part 2: The current approach to treatment. J. Respir. Dis., 28, 331-338.

Meyer, K.C. (2006). The aging human lung: age-associated changes in structure and function. In P. Michael Conn (Ed.), Handbook of Models for Human Aging. Burlington, MA: Elsevier Academic Press.

Meyer, K.C. (2005). Aging. Proc. Am. Thoracic Soc., 2, 433-439.

Neralla, S., & Meyer, K.C. (2005). The keys to the diagnosis of interstitial lung disease: Part 1. J. Respir. Disease, 26, 372-378 (Part 1), 443-448 (Part 2), 466-478 (Part 3).

Neralla, S., & Meyer, K.C. (2004). Drug treatment of pneumococcal infections in the elderly. Drugs and Aging, 21, 851-864.

Meyer, K.C. (2004). Pneumonia: Predisposing factors, prevention, and treatment. Geriatr. Times, 5, 12-13.

Meyer, K.C. (2004). Lung infections and aging. Ageing Res. Rev., 3(1), 55-67.
View publication via DOI: DOI:10.1016/j.arr.2003.07.002

Meyer, K.C. (2003). Interferon gamma-1b therapy for idiopathic pulmonary fibrosis: Is the cart before the horse? Mayo Clin. Proc., 78, 1073-1075.
View publication via DOI: DOI:10.4065/​78.9.1073

Reichmuth, K.J., & Meyer, K.C. (2003). Management of respiratory infection in the elderly. Ann. Long-Term Care, 11, 27-31 (Part 1) & 19-22 (Part 2).

Meyer, K.C. (2002). Lung immunology and host defense. Pulmonary Biology. In E.E. Bittar (Ed.), Health and disease. New York: Springer.

Meyer, K.C., & Zimmerman, J.J. (2002). Inflammation and surfactant. J. Pediatr. Respir. Res., 3, 308-14.
View publication via DOI: DOI:10.1016/S1043-6618(02)00212-8

Morrell, M.J., Arabi, Y., Zahn, B.R., Meyer, K.C., Skatrud, J.B., & Badr, M.S. (2002). Effects of surfactant on pharyngeal mechanics in sleeping humans: Implications for sleep apnea. Eur. Respir. J., 20, 451-457.
View publication via DOI: DOI:10.1183/09031936.02.00273702

Meyer, K.C., Cornwell, R.D., & Love, R.B. (2001). Short and long term results after lung volume reduction surgery. Opinion in Pulm. Med., 6, 116-121.

Meyer, K. (2001). The role of immunity in susceptibility to respiratory infection in the aging lung. Respir. Physiol., 128, 23-31.
View publication via DOI: DOI:10.1016/S0034-5687(01)00261-4

Meyer, K.C., Cardoni, A., & Xiang, Z. (2000). Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. J. Lab. Clin. Med., 135, 332-338.
View publication via DOI: DOI:10.1067/mlc.2000.105618

Meyer, K.C., & Soergel, P. (1999). Bronchoalveolar lymphocyte phenotypes change in the normal aging human lung. Thorax, 54, 697-700.
View publication via DOI: DOI:10.1136/thx.54.8.697

Meyer, K.C. (1999). Pathogenesis, diagnosis, and treatment of bronchiectasis. Pulm. Crit. Care. Update., 13, Lesson 21.

Meyer, K.C. (1998). Neutrophils and low-grade inflammation in the seemingly normal aging human lung. Mech. Aging Develop., 104, 169-81.
View publication via DOI: DOI:10.1016/S0047-6374(98)00065-7

Meyer, K.C., Ershler, W., Rosenthal, N., Lu, X., & Peterson, K. (1996). Immune dysregulation in the aging human lung. Am. J. Respir. Crit. Care Med., 153, 1072-1079.

Meyer, K.C. (1996). Therapy for idiopathic pulmonary fibrosis. Pulm. Crit. Care Update, 11, 1-8.

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