University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Stephen C. Lazarus, MD

Stephen C. Lazarus, MD

Professor, Department of Medicine (Pulmonary and Critical Care), UCSF

Research Summary

Dr. Lazarus is an inbred product of the University of California, having received his A.B. from Berkeley, his M.D. from Irvine, and training in Internal Medicine and Pulmonary & Critical Care Medicine at UCSF. Drafted into military service during the Viet Nam era, he spent 2 years as Chief of Pulmonary Medicine and Co-Director of the ICU at Andrews Air Force Base in Washington, D.C. before returning to UCSF for additional research training in the Cardiovascular Research Institute. Since joining the faculty at UCSF in 1983, Dr. Lazarus has directed basic and clinical research on the mechanisms and treatment of asthma, COPD, and other airway diseases. He is an Attending Physician on the Pulmonary Consult Service, the Adult Pulmonary Function Laboratory, and the Chest Faculty Practice at UCSF-Moffitt-Long Hospital, and has been Director of the Chest Faculty Practice, Director of the Medical Specialty Practices, and Interim Chief of the Division of Pulmonary and Critical Care Medicine. Currently he is Director of the Training Program in Pulmonary and Critical Care Medicine and Associate Director of the Adult Pulmonary Laboratory.

Research Interests:

Dr. Lazarus' research has focused on the role of inflammatory cells and mediators in regulating function of the lung and airways in obstructive lung diseases. After working in whole animals and organ systems, he developed continuous mastocytoma cell lines that share many important features of normal human mast cells. These cells served as a unique model system for mast cell biology as well as a source of mast cell-derived mediators to examine the role of these mediators in important biological processes.

Studies of mast cell mediators led to a series of investigator-initiated clinical research projects to examine the role of leukotrienes in chronic asthma and in mediating the bronchoconstrictor response to inhaled sulfur dioxide; the role of tachykinins in mediating the airway hyperresponsiveness, airway inflammation, and symptoms of chronic asthma; and the correlation between elastase and elastolytic activity in the sputum of patients with chronic bronchitis and physiological measures of lung function. In collaboration with Drs John Fahy, George Caughey, and Jay Nadel, Dr. Lazarus examined the effect of sputum proteases on airway inflammation, and the effect of inflammatory mediators on regulation of airway mucin gene expression and mucin secretion (via the EGF-receptor).

These studies provided the infrastructure for several successful competitive applications to the NIH to participate in Clinical Research Networks. In 1993, Drs. Boushey, Lazarus, and Fahy were awarded one of 6 Asthma Clinical Research Network (ACRN) Centers in the US, and their application was again successful in an open competition in 2003. This network conducts multicenter clinical trials to examine important mechanisms in the treatment and pathogenesis of asthma. In addition to serving on the Steering Committee of the Network, responsible for the design and implementation of all studies, Dr. Lazarus was the Lead Investigator on 2 major ACRN projects: one, a study that examined clinical outcomes and inflammatory biomarkers in subjects treated with inhaled corticosteroids or a long-acting ß-agonist, was published in JAMA, and was responsible for a change in asthma management guidelines. Dr. Lazarus also led a study that demonstrated that asthmatics who smoke have a blunted response to inhaled corticosteroids – apparently because smoking regulates transcription factors related to airway inflammation.

In 2003, Dr. Lazarus built upon studies of mucus hypersecretion and airway function to prepare a successful application to the NIH/NHLBI to participate as one of 7 sites in the COPD Clinical Research Network (CCRN). As Principal Investigator of this award, Dr. Lazarus led studies to examine biomarkers as predictors of COPD exacerbations, and to explore the role of arachidonic acid metabolites in the pathogenesis of COPD exacerbations. Dr. Lazarus Chairs the Steering Committee of this Network.

Dr. Lazarus is also Co-PI of the new (in 2009) AsthmaNet, an NHLBI network funded for 7 years to examine clinical outcomes and mechanisms of asthma. He is the lead investigator of a study of TH2 high vs TH2 low asthma phenotypes, to be launched in 2012.

Finally, in collaboration with Prescott Woodruff, Dr. Lazarus is a Co-Investigator of the new SPIROMICS network, an NHLBI-sponsored project to identify subpopulations of COPD patients that are similar with respect to molecular mechanisms of disease.

Selected Publications

  1. Ghosh S, Anderson WH, Putcha N, Han MK, Curtis JL, Criner GJ, Dransfield MT, Barr RG, Krishnan JA, Lazarus SC, Cooper CB, Paine R, Peters SP, Hansel NN, Martinez FJ, Drummond MB. Alignment of Inhaled COPD Therapies with Published Strategies: Analysis of the GOLD Recommendations in SPIROMICS. Ann Am Thorac Soc. 2018 Sep 14.
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  2. Jin M, Lee EC, Ra SW, Fishbane N, Tam S, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Aaron SD, Reed RM, Man SFP, Leung JM, Sin DD. Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD. Chest. 2018 Jul 03.
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  3. Durack J, Huang YJ, Nariya S, Christian LS, Mark Ansel K, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Rosenberg SR, King TS, White SR, Denlinger LC, Holguin F, Lazarus SC, Lugogo N, Peters SP, Smith LJ, Wechsler ME, Lynch SV, Boushey HA; ; 2018 Jun 9;6(1):104 Microbiome. 2018 Jun 9;6(1):104. doi: 10.1186/s40168-018-0487-3. PMID: 29885665 . Bacterial biogeography of adult airways in atopic asthma. Microbiome. 2018; 6:104.
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  4. Durack J, Huang YJ, Nariya S, Christian LS, Mark Ansel K, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Rosenberg SR, King TS, White SR, Denlinger LC, Holguin F, Lazarus SC, Lugogo N, Peters SP, Smith LJ, Wechsler ME, Lynch SV, Boushey HA. Bacterial biogeography of adult airways in atopic asthma. Microbiome. 2018 Jun 09; 6(1):104.
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  5. Lazarus SC. On-Demand versus Maintenance Inhaled Treatment in Mild Asthma. N Engl J Med. 2018 05 17; 378(20):1940-1942.
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  6. Sobieraj DM, Baker WL, Nguyen E, Weeda ER, Coleman CI, White CM, Lazarus SC, Blake KV, Lang JE. Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-analysis. JAMA. 2018 Apr 10; 319(14):1473-1484.
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  7. Sobieraj DM, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC, Blake KV, Lang JE, Baker WL. Association of Inhaled Corticosteroids and Long-Acting ß-Agonists as Controller and Quick Relief Therapy With Exacerbations and Symptom Control in Persistent Asthma: A Systematic Review and Meta-analysis. JAMA. 2018 Apr 10; 319(14):1485-1496.
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  8. Jackson DJ, Bacharier LB, Mauger DT, Boehmer S, Beigelman A, Chmiel JF, Fitzpatrick AM, Gaffin JM, Morgan WJ, Peters SP, Phipatanakul W, Sheehan WJ, Cabana MD, Holguin F, Martinez FD, Pongracic JA, Baxi SN, Benson M, Blake K, Covar R, Gentile DA, Israel E, Krishnan JA, Kumar HV, Lang JE, Lazarus SC, Lima JJ, Long D, Ly N, Marbin J, Moy JN, Myers RE, Olin JT, Raissy HH, Robison RG, Ross K, Sorkness CA, Lemanske RF. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations. N Engl J Med. 2018 03 08; 378(10):891-901.
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  9. Sobieraj DM, Baker WL, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC, Blake KV, Lang JE.. AHRQ Comparative Effectiveness Reviews. Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma [Internet]. 2018.
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  10. Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Leung JM, Paul Man SF, Aaron SD, Reed RM, Sin DD. Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD. Respir Res. 2018 Feb 14; 19(1):30.
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  11. Fawzy A, Putcha N, Paulin LM, Aaron CP, Labaki WW, Han MK, Wise RA, Kanner RE, Bowler RP, Barr RG, Hansel NN. Association of thrombocytosis with COPD morbidity: the SPIROMICS and COPDGene cohorts. Respir Res. 2018 Jan 26; 19(1):20.
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  12. Hastie AT, Martinez FJ, Curtis JL, Doerschuk CM, Hansel NN, Christenson S, Putcha N, Ortega VE, Li X, Barr RG, Carretta EE, Couper DJ, Cooper CB, Hoffman EA, Kanner RE, Kleerup E, O'Neal WK, Paine R, Peters SP, Alexis NE, Woodruff PG, Han MK, Meyers DA, Bleecker ER. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017 Dec; 5(12):956-967.
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  13. Han MK, Quibrera PM, Carretta EE, Barr RG, Bleecker ER, Bowler RP, Cooper CB, Comellas A, Couper DJ, Curtis JL, Criner G, Dransfield MT, Hansel NN, Hoffman EA, Kanner RE, Krishnan JA, Martinez CH, Pirozzi CB, O'Neal WK, Rennard S, Tashkin DP, Wedzicha JA, Woodruff P, Paine R, Martinez FJ. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017 08; 5(8):619-626.
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  14. Duffy S, Marron R, Voelker H, Albert R, Connett J, Bailey W, Casaburi R, Cooper JA, Curtis JL, Dransfield M, Han MK, Make B, Marchetti N, Martinez F, Lazarus S, Niewoehner D, Scanlon PD, Sciurba F, Scharf S, Reed RM, Washko G, Woodruff P, McEvoy C, Aaron S, Sin D, Criner GJ. Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD). Respir Res. 2017 Jun 19; 18(1):124.
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  15. Lugogo N, Green CL, Agada N, Zhang S, Meghdadpour S, Zhou R, Yang S, Anstrom KJ, Israel E, Martin R, Lemanske RF, Boushey H, Lazarus SC, Wasserman SI, Castro M, Calhoun W, Peters SP, DiMango E, Chinchilli V, Kunselman S, King TS, Icitovic N, Kraft M. Obesity's effect on asthma extends to diagnostic criteria. J Allergy Clin Immunol. 2018 Mar; 141(3):1096-1104.
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  16. Ra SW, Sze MA, Lee EC, Tam S, Oh Y, Fishbane N, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Aaron SD, Reed RM, Man SFP, Sin DD. Azithromycin and risk of COPD exacerbations in patients with and without Helicobacter pylori. Respir Res. 2017 May 30; 18(1):109.
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  17. Martinez CH, Murray S, Barr RG, Bleecker E, Bowler RP, Christenson SA, Comellas AP, Cooper CB, Couper D, Criner GJ, Curtis JL, Dransfield MT, Hansel NN, Hoffman EA, Kanner RE, Kleerup E, Krishnan JA, Lazarus SC, Leidy NK, O'Neal W, Martinez FJ, Paine R, Rennard SI, Tashkin DP, Woodruff PG, Han MK. Respiratory Symptoms Items from the COPD Assessment Test Identify Ever-Smokers with Preserved Lung Function at Higher Risk for Poor Respiratory Outcomes. An Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort. Ann Am Thorac Soc. 2017 May; 14(5):636-642.
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  18. Leitao Filho FS, Won Ra S, Mattman A, Schellenberg RS, Fishbane N, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Leung JM, Man SFP, Aaron SD, Reed RM, Sin DD. Serum IgG and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2017 Oct; 140(4):1164-1167.e6.
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  19. Nyenhuis SM, Krishnan JA, Berry A, Calhoun WJ, Chinchilli VM, Engle L, Grossman N, Holguin F, Israel E, Kittles RA, Kraft M, Lazarus SC, Lehman EB, Mauger DT, Moy JN, Peters SP, Phipatanakul W, Smith LJ, Sumino K, Szefler SJ, Wechsler ME, Wenzel S, White SR, Ackerman SJ. Race is associated with differences in airway inflammation in patients with asthma. J Allergy Clin Immunol. 2017 Jul; 140(1):257-265.e11.
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  20. Durack J, Lynch SV, Nariya S, Bhakta NR, Beigelman A, Castro M, Dyer AM, Israel E, Kraft M, Martin RJ, Mauger DT, Rosenberg SR, Sharp-King T, White SR, Woodruff PG, Avila PC, Denlinger LC, Holguin F, Lazarus SC, Lugogo N, Moore WC, Peters SP, Que L, Smith LJ, Sorkness CA, Wechsler ME, Wenzel SE, Boushey HA, Huang YJ. Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment. J Allergy Clin Immunol. 2017 Jul; 140(1):63-75.
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