Stephen C. Lazarus, MD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Stephen C. Lazarus, MD

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

Phone: (415) 353-2961 (appts)
Box 0111, UCSF
San Francisco, CA 94143-0111

UCSF Profiles | Physician Referral Directory

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. 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 M, 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. 2016 Nov 9.
    View on PubMed
  2. Sadatsafavi M, Sin DD, Zafari Z, Criner G, Connett JE, Lazarus S, Han M, Martinez F, Albert R. The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model. Am J Epidemiol. 2016 Nov 1; 184(9):681-689.
    View on PubMed
  3. Leung JM, Chen V, Hollander Z, Dai D, Tebbutt SJ, Aaron SD, Vandemheen KL, Rennard SI, FitzGerald JM, Woodruff PG, Lazarus SC, Connett JE, Coxson HO, Miller B, Borchers C, McManus BM, Ng RT, Sin DD. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry. PLoS One. 2016; 11(8):e0161129.
    View on PubMed
  4. Bhatt SP, Connett JE, Voelker H, Lindberg SM, Westfall E, Wells JM, Lazarus SC, Criner GJ, Dransfield MT. ß-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (ßLOCK COPD): a randomised controlled study protocol. BMJ Open. 2016; 6(6):e012292.
    View on PubMed
  5. Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, Gouskova NA, Hansel NN, Hoffman EA, Kanner RE, Kleerup E, Lazarus SC, Martinez FJ, Paine R, Rennard S, Tashkin DP, Han MK. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. N Engl J Med. 2016 May 12; 374(19):1811-21.
    View on PubMed
  6. Bacharier LB, Guilbert TW, Mauger DT, Boehmer S, Beigelman A, Fitzpatrick AM, Jackson DJ, Baxi SN, Benson M, Burnham CA, Cabana M, Castro M, Chmiel JF, Covar R, Daines M, Gaffin JM, Gentile DA, Holguin F, Israel E, Kelly HW, Lazarus SC, Lemanske RF, Ly N, Meade K, Morgan W, Moy J, Olin T, Peters SP, Phipatanakul W, Pongracic JA, Raissy HH, Ross K, Sheehan WJ, Sorkness C, Szefler SJ, Teague WG, Thyne S, Martinez FD. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial. JAMA. 2015 Nov 17; 314(19):2034-44.
    View on PubMed
  7. Dunn RM, Lehman E, Chinchilli VM, Martin RJ, Boushey HA, Israel E, Kraft M, Lazarus SC, Lemanske RF, Lugogo NL, Peters SP, Sorkness CA, Szefler S, Wechsler ME. Impact of Age and Sex on Response to Asthma Therapy. Am J Respir Crit Care Med. 2015 Sep 1; 192(5):551-8.
    View on PubMed
  8. Wang Y, Tong C, Wang Z, Wang Z, Mauger D, Tantisira KG, Israel E, Szefler SJ, Chinchilli VM, Boushey HA, Lazarus SC, Lemanske RF, Wu R. Pharmacodynamic genome-wide association study identifies new responsive loci for glucocorticoid intervention in asthma. Pharmacogenomics J. 2015 Oct; 15(5):422-9.
    View on PubMed
  9. Ono E, Dutile S, Kazani S, Wechsler ME, Yang J, Hammock BD, Douda DN, Tabet Y, Khaddaj-Mallat R, Sirois M, Sirois C, Rizcallah E, Rousseau E, Martin R, Sutherland ER, Castro M, Jarjour NN, Israel E, Levy BD. Lipoxin generation is related to soluble epoxide hydrolase activity in severe asthma. Am J Respir Crit Care Med. 2014 Oct 15; 190(8):886-97.
    View on PubMed
  10. Han MK, Tayob N, Murray S, Dransfield MT, Washko G, Scanlon PD, Criner GJ, Casaburi R, Connett J, Lazarus SC, Albert R, Woodruff P, Martinez FJ. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014 Jun 15; 189(12):1503-8.
    View on PubMed
  11. Criner GJ, Connett JE, Aaron SD, Albert RK, Bailey WC, Casaburi R, Cooper JA, Curtis JL, Dransfield MT, Han MK, Make B, Marchetti N, Martinez FJ, Niewoehner DE, Scanlon PD, Sciurba FC, Scharf SM, Sin DD, Voelker H, Washko GR, Woodruff PG, Lazarus SC. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014 Jun 5; 370(23):2201-10.
    View on PubMed
  12. Castro M, King TS, Kunselman SJ, Cabana MD, Denlinger L, Holguin F, Kazani SD, Moore WC, Moy J, Sorkness CA, Avila P, Bacharier LB, Bleecker E, Boushey HA, Chmiel J, Fitzpatrick AM, Gentile D, Hundal M, Israel E, Kraft M, Krishnan JA, LaForce C, Lazarus SC, Lemanske R, Lugogo N, Martin RJ, Mauger DT, Naureckas E, Peters SP, Phipatanakul W, Que LG, Sheshadri A, Smith L, Solway J, Sullivan-Vedder L, Sumino K, Wechsler ME, Wenzel S, White SR, Sutherland ER. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014 May; 311(20):2083-91.
    View on PubMed
  13. Woodruff PG, Chatila W, Connett JE, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Marchetti N, Rogers TJ, Scanlon PD, Sin DD, Voelker H, Wendt C, Albert RK. Tumour necrosis factor receptor-75 and risk of COPD exacerbation in the azithromycin trial. Eur Respir J. 2014 Jan; 43(1):295-8.
    View on PubMed
  14. Peters SP, Bleecker ER, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Craig T, Denlinger LC, Engle LL, Dimango EA, Israel E, Kraft M, Lazarus SC, Lemanske RF, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness CA, Sutherland ER, Wasserman SI, Walter MJ, Wechsler ME, Chinchilli VM, Szefler SJ. Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol. 2013 Nov; 132(5):1068-1074.e1.
    View on PubMed
  15. Couper D, LaVange LM, Han M, Barr RG, Bleecker E, Hoffman EA, Kanner R, Kleerup E, Martinez FJ, Woodruff PG, Rennard S. Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS). Thorax. 2014 May; 69(5):491-4.
    View on PubMed
  16. Albert RK, Connett J, Curtis JL, Martinez FJ, Han MK, Lazarus SC, Woodruff PG. Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2012; 7:767-77.
    View on PubMed
  17. Denlinger LC, Manthei DM, Seibold MA, Ahn K, Bleecker E, Boushey HA, Calhoun WJ, Castro M, Chinchili VM, Fahy JV, Hawkins GA, Icitovic N, Israel E, Jarjour NN, King T, Kraft M, Lazarus SC, Lehman E, Martin RJ, Meyers DA, Peters SP, Sheerar D, Shi L, Sutherland ER, Szefler SJ, Wechsler ME, Sorkness CA, Lemanske RF. P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy. Am J Respir Crit Care Med. 2013 Jan 1; 187(1):28-33.
    View on PubMed
  18. Brozek JL, Kraft M, Krishnan JA, Cloutier MM, Lazarus SC, Li JT, Santesso N, Strunk RC, Casale TB. Long-acting ß2-agonist step-off in patients with controlled asthma. Arch Intern Med. 2012 Oct 8; 172(18):1365-75.
    View on PubMed
  19. Calhoun WJ, Ameredes BT, King TS, Icitovic N, Bleecker ER, Castro M, Cherniack RM, Chinchilli VM, Craig T, Denlinger L, DiMango EA, Engle LL, Fahy JV, Grant JA, Israel E, Jarjour N, Kazani SD, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF, Lugogo N, Martin RJ, Meyers DA, Moore WC, Pascual R, Peters SP, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Wasserman SI, Walter MJ, Wechsler ME, Boushey HA. Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA. 2012 Sep 12; 308(10):987-97.
    View on PubMed
  20. Dransfield MT, Harnden S, Burton RL, Albert RK, Bailey WC, Casaburi R, Connett J, Cooper JA, Criner GJ, Curtis JL, Han MK, Make B, Marchetti N, Martinez FJ, McEvoy C, Nahm MH, Niewoehner DE, Porszasz J, Reilly J, Scanlon PD, Scharf SM, Sciurba FC, Washko GR, Woodruff PG, Lazarus SC. Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in chronic obstructive pulmonary disease. Clin Infect Dis. 2012 Sep; 55(5):e35-44.
    View on PubMed

Go to UCSF Profiles, powered by CTSI