Gary A. Salzman, M.D.
Professor, Senior Docent
Department(s) of Internal Medicine
Section: Respiratory and Critical Care
UMKC School of Medicine, University Health - UMKC Health Sciences District
Education and Background
University of Missouri - Kansas City
Residency - Internal Medicine - Wake Forest University
Fellowship - Pulmonary - University of Missouri - Kansas City
Meet Gary SalzmanWere you always focused on being a doctor growing up?
No, I originally wanted to be an astronaut when I saw Neil Armstrong walking on the moon. But that was nixed when I got motion sickness at the amusement park, and I thought, well, astronaut is off of the list. It was not an option after that. I was interested in sports. I played basketball and ran track. I was very interested in sports growing up.Why UMKC School of Medicine?
I like the opportunity to mentor medical students, to be a docent, and develop a relationship with a small group of students. That extends to being the program director for the pulmonary and critical care fellowship. I have nine fellows that I work with and mentor. I’ve had some great mentors in my time. William Sirridge was one of them. Now at this point in my career, I’m mentoring junior faculty and all of that is very enjoyable and rewarding to me.What do you like to do when you’re not at work?
My wife and I like to travel. We also have a two-year-old grandson and spend a lot of time with him. I play golf and some tennis. I’m also involved in the Big Brothers and Big Sisters program. We had a bowling fundraiser for Big Brothers recently, so actually all of my students went bowling that night for the Big Brothers organization.
Pulmonary and critical care medicine
Clinical research is focused on methods of new treatments for asthma, pulmonary fibrosis and chronic obstructive pulmonary disease.
In 1999 UMKC School of Medicine led by Gary A. Salzman MD, FCCP in partnership with Truman Medical Center and Children’s Mercy Hospital established the UMKC Asthma Clinical Research Center (ACRC) funded by a $500,000 grant over five years from the American Lung Association (ALA). In 2004 UMKC was awarded increased funding from the American Lung Association of $750,000 over 5 years. Recently funding was extended for another 3 years until 2012. The American Lung Association- Asthma Clinical Research Centers (ALA-ACRC) has successfully completed five clinical trials with several additional trials under way or in preparation. Currently there are 17 clinical centers and a data coordinating center at Johns Hopkins University.
Why did the ALA fund this large network? Health care providers caring for patients with asthma need answers quickly to provide the best care for their patients. Clinical studies performed at one center or even three or four centers may take up to five years to enroll enough subjects to answer such important questions.
The ALA recognized that 17 clinical centers will be able to enroll a large number of subjects in a relatively short period of time so the studies’ results can be published and health care providers can have the answers they need to provide the best evidence-based care to their patients with asthma.
Another advantage of a large network of clinical centers is the ability to enroll subjects from diverse populations. The populations represented in the ALA-ACRC studies include the same type of patients encountered by health care providers across the country.
Five practical and clinically important questions addressed by the ALA-ACRC are summarized below.
Is the influenza vaccine safe for patients with asthma?
The ALA-ACRC Network’s first endeavor was the Study of Inactivated Influenza Vaccine in Asthmatics (SIIVA). Influenza causes substantial morbidity in adults and children with asthma. However, the rate of vaccination for patients with asthma has been low partly due to fears of increased exacerbations from the vaccine.
The purpose of SIIVA was to evaluate the safety of the influenza vaccine in patients with asthma. The trial enrolled 2,032 participants in a three-month period between September and November 2000. Results showed rates of asthma exacerbations between vaccine and placebo injections were equivalent in a diverse population of adults and children with asthma, including severe asthma. The results were published in the New England Journal of Medicine.
Health care providers should encourage patients with asthma to be immunized. Not only is the vaccine safe in this population, but vaccination also reduces the morbidity and mortality associated with influenza in patients with asthma.
Add-on controller medications
Which add-on controller medications work well for patients with uncontrolled asthma?
The ALA-ACRC Network’s second clinical trial was the Effectiveness of Low Dose Theophylline as Add-On Therapy in Treatment of Asthma (LODO). Current guidelines recommend adding a controller medication to the treatment regimen of poorly controlled patients with asthma. Theophylline, a relatively inexpensive asthma medication, and anti-leukotriene agents such as montelukast, are convenient choices because both are once-a-day medications taken by mouth.
The comparative effectiveness of these two add-on treatments for poorly controlled asthma is unknown. LODO is the first clinical trial to directly compare theophylline to both active (montelukast) and placebo control.
The study enrolled 489 adolescents and adults with poorly controlled asthma over an 11-month period between 2001 and 2002. The primary outcome was the rate of episodes of poor asthma control (EPACs). An EPAC is a composite measure of asthma control including measures of asthma control, need for medical care, and lung function.
Results showed neither low-dose theophylline nor montelukast decreased the rate of EPACs in patients with poorly controlled asthma as compared to the placebo group. Both treatments did, however, improve lung function as measured by spirometry.
In a sub-group of patients not taking inhaled corticosteroids (ICS), monotherapy low-dose theophylline resulted in both statistically and clinically significant improvements in asthma control and symptoms. Montelukast was less effective in patients not on an ICS. As such, low-dose theophylline may provide an effective, safe and low-cost treatment alternative for patients with poorly controlled asthma who can’t or won’t use ICS because of side effects, preference, or cost.
Which step-down therapy options work well for patients with mild asthma?
Current guidelines for the treatment of patients with mild persistent asthma are to establish control of symptoms using inhaled corticosteroids and then “step-down” therapy to the minimum needed to maintain control. Although step-down therapy has been studied in patients with moderate to severe asthma, it hasn’t been systematically evaluated in patients with mild asthma. This was the purpose of the Leukotriene Modifier or Corticosteroids or Corticosteroid-Salmeterol (LOCCS) trial.
A large number of patients with asthma have a mild form of the disease. Encouraging patient adherence to asthma treatment regimens continues to present challenges. Providing patients with convenient, efficacious alternative treatments associated with fewer side effects could enhance adherence and reduce unnecessary medication exposure.
This clinical trial compared three alternative treatments for patients whose asthma was well controlled on low-dose inhaled corticosteroids. The treatment groups were fluticasone (100 mg twice a day), fluticasone plus salmeterol (100/50 mg once daily) or montelukast (10 mg or 5 mg daily for adults and children, respectively). The study randomized 500 children and adults; participant follow-up was completed in July 2005.
Results showed patients with asthma well controlled on twice-daily inhaled fluticasone can be stepped-down to once daily fluticasone/salmeterol without increased rates of treatment failure.
Stepping-down to montelukast resulted in an increase in treatment failures and decreased asthma control. Notably, however, there were a high number of symptom-free days for patients in all treatment groups, including 79 percent of days for patients taking montelukast over a four-month follow-up period. Hence, oral montelukast isn’t as effective as either low-dose ICS (twice a day) or a low-dose ICS with salmeterol (once daily), but montelukast still provided good asthma control for most patients. The results were published in the New England Journal of Medicine.
Are the effects of patient education real or not?
The Trial of Asthma Patient Education (TAPE) was designed to evaluate the effect of patient education on the treatment response to both placebo and montelukast. The National Heart Lung Blood Institute-funded trial completed enrollment in 2005, eight months ahead of schedule.
Patients randomized to montelukast or placebo was randomized again to receive either an enhanced presentation of the study treatment or a neutral presentation. The enhanced presentation was designed to increase expectancy of therapeutic benefit.
We compared effects of the enhanced presentation independently in the montelukast and placebo groups. This comparison addressed the question — does increasing expectancy improve outcomes equally in active treatment and placebo groups?
The usual care group was compared to the placebo group receiving the neutral presentation to estimate the placebo effect. Results showed the placebo and education effects were small for measures of lung function. However, there were effects on symptom indices such as Asthma Control Score.
Furthermore, “nocebo” effects were observed on side effects, such that more patients reported headache in the placebo group after receiving information about possible side effects than those on placebo who didn’t receive similar information. These results address the specific question about the best ways to evaluate new therapies for asthma and, more generally, how the use of placebo may affect the results of clinical trials.
The main results of the trial are currently being prepared for publication as well as results from several sub-studies evaluating adherence and education effects.
GERD & asthma
Can treatment with a proton pump inhibitor (PPI) of gastroesophogeal reflux disease improve asthma control?
GERD is common in patients with asthma, even in patients who have no symptoms of heartburn. It’s predicted that GERD may contribute to poor control of asthma but its unknown if empiric treatment of GERD in patients with poorly controlled asthma can improve control.
Two complementary clinical trials funded by the NHLBI in adults and children were conducted by the ALA-ACRC. Both trials examine whether treatment with a PPI for GERD will improve asthma control in patients with poorly controlled asthma despite relatively high doses of inhaled steroids. Subjects undergo esophageal pH monitoring for the accurate diagnosis of GERD and have methacholine challenge testing to determine changes in bronchial reactivity. The adult study was completed in 2009 and demonstrated no improvement in asthma control with high dose proton pump inhibitor treatments. The results were published in the New England Journal of Medicine. The pediatric study will be completed in 2011.
The ALA-ACRC has provided answers to important clinical questions for health care providers working in the trenches caring for asthma patients every day. Investigators on the ALA-ACRC steering committee are planning several future studies to improve the quality of life for adults and children living with asthma. We recently have acquired funding from the NIH for two additional studies. One study evaluates the administration of Soy supplements to uncontrolled asthmatics to determine if there is improved asthma control. The other study evaluates the treatment of allergic rhinitis/sinusitis on asthma control.
The UMKC ACRC is one 17 centers nationwide undertaking a multi-center research approach to discovering improved methods to manage asthma with the long term goal to find a cure for asthma. UMKC joins Johns Hopkins, Duke, Washington University in St. Louis, and many other prestigious universities in the largest industry independent research consortium to ever study asthma.
UMKC Lung Research Center
The Lung Research Center at UMKC was started by Dr. Salzman in 2005 to expand on the successes in clinical asthma research to include collaboration with UMKC basic science researchers. Areas of planned studies include metabolic bone disease related to the use of systemic corticosteroids, discovery of novel mechanisms of disease in sarcoidosis, lung injury related to fat embolism from long bone fractures, and the genetic characteristics of asthma.
The collaboration of the clinical and basic science investigators with expertise in many aspects of lung disease will lead to significant discoveries that will be taken from bench to bedside to improve the treatment for many types of lung disease. The addition of an endowed chair in lung research will serve as a catalyst for the expansion of research activities and funding. Building on the strong foundation of existing funding and the talent of existing faculty the UMKC Lung Research Center will obtain international prominence in the next five years.
The American Lung Association Asthma clinical Research Centers (including GA Salzman). Clinical Trial of Low-dose Theophylline and Montelukast in Patients with Poorly Controlled Asthma. AJRCCM 2007. 175:235-242
The American Lung Association Asthma Clinical Research Centers (including GA Salzman). Randomized Comparison of Strategies for Reducing Treatment in Mild Persistent Asthma. N Eng J Med 2007; 356:2027-2039
Salzman GA. Smoking Ruins, The Prevention of Lung Disease. Missouri Medicine 2007; 104 (3): 208-209.
Khan ZU, Salzman GA. Management of Sepsis: The Surviving Sepsis Guidelines for Early Therapy. Hospital Physician 2007; 55:21-30.
The American Lung Association Asthma Clinical Research Center (including GA Salzman). Efficacy of Esomeprazole for Treatment of Poorly Controlled Asthma. N Engl J Med 2009;360:1487-99.
M Das, GA Salzman. Pulmonary Alveolar Proteinosis: An Overview for Internists and Hospital Physicians. Hospital Practice 2010;38(1):277-280.
Cox LS, Faseru B, Mayo MS, Krebill R, Snow TS, Bronars CA, Nollen NL, Choi WS, Okuyemi KS, Salzman GA, Benowitz NL, Tyndale RF, Ahluwalia JS. Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data. Trials 2011, 12:22
Jallu SS, Salzman GA. A Case-Based Approach to Noninvasive Positive Pressure Ventilation. Hospital Practice 2011; 39(3):168-175.
The American Lung Association Asthma Clinical Research Center (including GA Salzman). Lansoprazole for Children with Poorly Controlled Asthma. JAMA. 2012;307(4):373-381
Saettele TM, Mohr J. Evaluation and Management of Acute Kidney Injury in the Intensive Care Unit. Missouri Medicine 2012:109(5):379-383
The Leukotriene Modifier Or Corticosteroids Trial (The LOCS Trial):
A Comparison of Continued Low-Dose Inhaled Corticosteroids versus Leukotriene Modifier for Asthmatic Patients Well Controlled with Low Dose Inhaled Corticosteroids, Principal investigator. Funding from GlaxoSmithKline $4,633,888 total funding over 5 years to Asthma Clinical Research Centers 2001-2006 One of 19 principal investigators.
The Trial of Asthma Patient Education, Funding from National Heart, Blood and Lung Institute $2,570,617 total funding over 4 years to Asthma Clinical Research Centers 2002-2006. One of 19 principal investigators
Study of Acid Reflux in Asthma, Funding from National Heart, Blood and Lung Institute $3,800,627 total funding over 5 years to Asthma Clinical Research Centers 2004-2009. One of 19 principal investigators
Study of Acid Reflux in Childhood Asthma, Funding from National Heart, Blood and Lung Institute $2,414,841 total funding over 5 years to Asthma Clinical Research Centers 2007-2012 One of 20 principal investigators
American Lung Association: Asthma Clinical Research Center: 2009-2012 for $300,000. Principal Investigator
Missouri Hospital Association Regional Health Partnership Grant for Asthma Education and Research Programs- $100,000; 2002-2006. Principal Investigator
Blue Cross and Blue Shield of Kansas City: $49,875. Developing a culturally tailored smoking cessation program for heavily addicted Chronic Obstructive Pulmonary Disease (COPD) patients; Principal Investigator 2007-2009
American Lung Association Asthma Clinical Research Centers (ACRC)
The Study of Soy Isoflavones in Asthma (SOYA) National Heart, Blood and Lung Institute: R01 HL0088367-01A2- total funding $1.5 million- one of 18 ACRC multi-center co-investigators 2010-2013
American Lung Association Asthma Clinical Research Centers (ACRC) Study of Asthma and Nasal Steroids (STAN) National Heart, Blood and Lung Institute: U01 HL00895101-01A2- total funding $2.1
One of 18 ACRC multi-center co-investigators 2010-2013
Geldmacher Pulmonary Fibrosis Research Center 2012-2017 $400,000 Principal Investigator