Diseases involving the immune system affect millions of Americans, resulting in considerable pain and suffering, medical expense, and decreased quality of life. The National Institute of Allergy and Infectious Diseases (NIAID) seeks to improve the health status of the Nation’s ethnic minority populations through support for basic and clinical research, demonstration and education research projects, and minority health resource development.

NIAID supports research, education, and community outreach activities directed at certain health problems that disproportionately affect minority populations. NIAID’s objectives with respect to minority health in the areas of allergy, immunology, and transplantation are as follows:

• To support basic and clinical research directed at certain health problems as they affect minority populations (e.g., asthma, systemic lupus erythematosus, and end-stage kidney disease).
• To support demonstration and education research aimed at reducing the severity and incidence of certain health problems among minorities through the design and testing of the effectiveness of interventions.
• To increase the number of minority biomedical scientists through individual and institutional support for undergraduate, graduate, and postgraduate research training in a variety of disciplines relating to disorders of the immune system.

Asthma and Allergic Diseases

Asthma is an inflammatory lung disease. The cellular infiltrates and inflammatory mediators of asthma are thought to be similar to those of other allergic diseases, but the mediators apparently also cause airway hyperreactivity. Although allergic reactions are an important cause of asthma, nonimmunologic factors, such as viral infections and exposure to environmental tobacco smoke and pollutants, also contribute to the pathophysiology of this disease.

Asthma causes significant morbidity and enormous economic costs. Asthma morbidity and mortality have been increasing in the United States for the past 15 years, and asthma morbidity and mortality are particularly high among poor, African American and Hispanic/Latino inner-city residents. Low socioeconomic status, exposure to cockroach allergens and pollutants, lack of access to medical care, and lack of self-management skills all contribute to increased morbidity from asthma. More than 50 million Americans, 1 out of every 5, are reactive to at least 1 of 8 selected allergens known to contribute to allergic illness.

The prevalence of asthma in 1994 was estimated to be 14.6 million persons (approximately 5.6 percent of the population) in the United States, of whom nearly 4.8 million (6.9 percent) were children 17 years old and younger, and asthma was the first-listed diagnosis for more than 468,000 hospitalizations. Asthma is more prevalent among African American children who are 6 to 11 years old than among white children of the same age (9.4 and 6.2 percent, respectively). The prevalence of asthma has increased approximately 40 percent among U.S. children under 18 years of age during the decade of the 1980’s. Although deaths from asthma are infrequent, mortality rates for all ages increased 46 percent during the 1980’s (1.3 per 100,000, or 2,891 deaths, to 1.9 per 100,000, or 4,867 deaths). Among 0- to 24-year-olds, deaths from asthma increased 118 percent between 1980 and 1993. Among 5- to 34-year-olds, nonwhites were two to three times as likely as whites to die from asthma.

The economic costs of asthma are enormous, with an estimated cost in the United States in 1990 of $6.2 billion. The largest single indirect cost was $1 billion for decreased productivity due to loss of schooldays. Despite the widespread assumption that asthma is a mild illness, 43 percent of the cost was due to emergency room use, hospitalization, and death.

In response to this recent rise in asthma morbidity among nonwhite populations, NIAID initiated the National Cooperative Inner-City Asthma Study (NCICAS) in FY 1991. NCICAS was composed of eight study units that engaged in a seven-city study aimed at improving morbidity of asthma among inner-city children. The eight centers were Albert Einstein School of Medicine, New York, New York; Johns Hopkins University, Baltimore, Maryland; Children’s Memorial Hospital, Chicago, Illinois; Mt. Sinai Medical Center, New York, New York; Case Western Reserve University, Cleveland, Ohio; Henry Ford Hospital, Detroit, Michigan; Howard University, Washington, D.C.; and Washington University, St. Louis, Missouri.

Phase I of NCICAS began in November 1992 and ended in June 1994. The objective of NCICAS phase I was to identify intervenable factors determining asthma severity and morbidity among inner-city children. During phase I, 1,528 participants ages 4 to 9 years were recruited from both emergency rooms and primary care clinics at the 8 sites. The participants had a comprehensive examination, which included pulmonary functions, allergen skin tests, and urinary cotinine to monitor exposure to environmental tobacco smoke. Information was collected on asthma severity, access to health care, compliance with medical therapy, psychosocial issues, living conditions, and the economic cost of asthma treatment. Over 90 percent of the participants were followed at 3, 6, and 9 months to monitor asthma morbidity prospectively. Home environmental surveys, which measured allergen exposure (dust mite, cat, cockroach) and home nitrogen dioxide levels, were completed in more than 660 homes.

The phase I population was approximately 20 percent Hispanic/Latino and 73 percent African American, with the remainder white. A high level of asthma morbidity was experienced by these children. The phase I results include:

• Knowledge about asthma is high, but asthma self-management skills are poor.
• Cockroach may be the most important allergen among inner-city children with asthma. Cockroach allergen levels are high, and a higher proportion of inner-city children are sensitive to cockroach than to dust mite and other allergens. In contrast, cockroach is a minor allergen in children with asthma who live in the suburbs.
• Asthma severity correlates with the degree of cockroach sensitivity and sensitivity in turn correlates with the levels of cockroach allergen exposure.

NCICAS phase II ran from November 1994 to January 1996. This phase of the study evaluated the cost-effectiveness of an asthma counselor in reducing the excessive burden of asthma morbidity. More than 1,030 inner-city patients with asthma and their families participated in the phase II intervention. Over 90 percent completed the intervention. Three of the phase II sites have adopted the intervention strategy for use with Spanish-speaking children. Preliminary results of the evaluation are expected in winter 1996.

NIAID and the National Institute of Environmental Health Sciences (NIEHS) are cosponsoring a multicenter study to refine and evaluate NCICAS I with particular emphasis on the environmental components. The study, called the National Cooperative Inner-City Asthma Study II, began in September 1996 and will be completed in 5 years. Seven sites and a data center are participating: Children’s Memorial Hospital, Chicago, Illinois; Arizona Health Sciences Center, Tucson, Arizona; Albert Einstein College of Medicine, Bronx, New York; Boston University School of Medicine, Boston, Massachusetts; Mount Sinai School of Medicine, New York, New York; University of Texas Southwestern Medical Center, Dallas, Texas; Odessa Brown Children’s Clinic, Seattle, Washington; and New England Research Institute, Watertown, Massachusetts.

In FY 1996, NIAID supported an intramural and 15 extramural Asthma, Allergy, and Immunologic Disease Cooperative Research Centers (AAIDCRC). These centers’ Asthma Demonstration and Education projects focus on local minority communities to better understand the reasons for the high levels of asthma morbidity and to evaluate interventions attempting to reduce asthma morbidity in these communities. One of these centers, at the University of California in Los Angeles, is funded in collaboration with NIEHS. This center is focused on the role of environmental factors in the pathogenesis of asthma and allergic diseases.

The 15 AAIDCRC demonstration and education projects aim to develop and evaluate innovative ways to treat and prevent asthma or immunologic diseases in underserved populations, mostly of ethnic minorities. The project at the Medical College of Virginia, Richmond, is evaluating an education program aimed at African American patients with systemic lupus erythematosus.

Other NIAID-supported projects conducted in FY 1996-97 include the following:

• Asthma Risk Factors and Management is being supported at the Johns Hopkins University, Baltimore, Maryland. This project evaluates the impact of race and socioeconomic factors on severity of asthma among inner-city African American adolescents.
• Project Head Start: Identifying Children at High Risk for Asthma With Increased Morbidity is being conducted at the University of Wisconsin, Madison, Wisconsin. This project is implementing the Open Airways asthma education program for children with asthma who are identified through the Head Start program.
• The House Dust Avoidance Measures in Inner-City Children With Asthma study is being conducted at four sites: University of Virginia, Charlottesville, Virginia; University of Alabama, Birmingham, Alabama; University of Washington, Seattle, Washington; and Mayo Clinic, Rochester, Minnesota. This four-site project is conducting a randomized, placebo-controlled trial of mite allergen avoidance among poor urban and rural patients with asthma.
• The Effect of Cockroach Allergens in Children With Asthma project is being conducted at Duke University, Durham, North Carolina. The study involves measuring the cockroach infestation and allergen levels in homes of minority inner-city children in North Carolina.
• The Morehouse University Clinic-Based Asthma Intervention Program is evaluating the A+ Asthma education program among inner-city children in Atlanta, Georgia.
• Asthma Self-Management, a School-Based Educational and Behavioral Intervention, at the University of Miami, Florida, evaluates a school-based asthma intervention program aimed at Cuban-American children.
• Asthma Education and Management in a Latino Neighborhood at Children’s Hospital, Boston, Massachusetts, is evaluating the A+ Asthma Club in a school-based asthma intervention among inner-city children.
• The Multisite Protocol for the Spanish Version of Asthma Control and Treatment for Children (ACT-PN), at the University of Chicago, Chicago, Illinois, and the University of Texas, Dallas, Texas, is a two-site randomized, control trial evaluating ACT-PN among inner-city Hispanic/Latino children.

NIAID participated in the AAIDCRC Demonstration and Education Project Directors meeting held in March 1996 at the American Academy of Allergy, Asthma, and Immunology meeting in New Orleans, Louisiana. This meeting reviewed progress of the demonstration and education projects of the centers and focused on strategies to improve recruitment and retention of study subjects. It also focused on the role in asthma of allergens, pollutants, and environmental tobacco smoke. Also discussed was the four-center demonstration project on the effect of dust mite allergen avoidance on asthma.

Autoimmune Diseases

The autoimmune disorders can be divided into two main groups: organ-specific and non-organ-specific diseases. Organ-specific diseases are characterized by immune reactions and tissue damage localized to a single organ or tissue, for example, type I diabetes mellitus and multiple sclerosis, where the primary lesions are localized in the pancreas and the central nervous system, respectively. In contrast, non-organ-specific diseases such as systemic lupus erythematosus (SLE) are characterized by immune reactivity against antigens distributed throughout the body, and this results in widespread damage. SLE is estimated to affect 131,000 Americans, 90 percent of whom are women of childbearing age.

Systemic lupus erythematosus is more common and severe in African American women than other ethnic groups. NIAID funds a small epidemiologic study to investigate the prevalence of the disease in women in Africa and the Caribbean and in African American women in the United States. This information may provide clues concerning the genetic and environmental factors important in the pathogenesis of this disease. NIAID also supports a demonstration and education project addressing the effects of educating patients with SLE, particularly African American patients, about the complications of this disease.

Transplantation

NIAID research in the field of transplantation encompasses a variety of basic and clinical research efforts focused on addressing the higher incidence rates of end-stage renal disease (ESRD) among minority populations. These efforts include a cooperative clinical trial to test new modalities of immunosuppression to prevent kidney graft rejection; the screening, characterization, and acquisition of reagents for histocompatibility testing of transplantation antigens for African Americans, Hispanics/Latinos, and Native Americans; and support for several Transplantation Program projects and investigator-initiated studies involving immunologic mechanisms and potential immunotherapies in the prevention of graft rejection.

Today, hemodialysis, peritoneal dialysis, and renal transplantation are life-saving treatment modalities for patients with partial or complete renal failure. However, the rate of occurrence of ESRD, specifically in minorities, continues to increase by more than 8 percent per year, with immunologic diseases being responsible for a significant number of new ESRD cases. The incidence of IDDM, an autoimmune disease that can lead to renal failure, has increased at an average rate of 13 percent per year for the last 5 years, while glomerulonephritis, a heterogeneous group of immunologic diseases that target the glomerulus (the filtering unit of the kidney), continues to be the third major cause of ESRD.

Nearly 19,000 kidney transplants are performed each year in the United States. Transplantation is clearly the treatment of choice for ESRD because 60 percent of dialysis patients die within 3 months to 5 years.

Therefore, research supported by NIAID is targeted at both the development of improved, specific immunosuppressive agents and the understanding and development of strategies to induce donor-specific tolerance in the transplant recipient that would allow discontinuation of nonspecific immunosuppression.

In 1995, 19,136 organ transplants were performed in the United States. Transplants included 10,891 kidneys, 3,922 livers, 2,361 hearts, 110 pancreata, 871 lungs, 67 heart-lung combinations, and 914 combined kidney-pancreas.

In 1993, 217,479 Americans with ESRD required treatment with dialysis (180,127) or transplantation (11,021). Reimbursements for all treatment modalities for ESRD beneficiaries totaled $11.1 billion in 1994; $8.3 billion was from Medicare while $1.8 billion was from third-party payers. As a comparison, the average cost for all Medicare services from 1991 to 1993 was $36,700 per year at risk per patient. For all dialysis patients total Medicare payment for the same period was $43,700 per year at risk, whereas for transplant patients it was $17,600 per year. In addition, the life expectancy of ESRD patients is one-fourth to one-fifth that of the U.S. general population.

There is a racial disparity in renal transplantation rates. Although African Americans represent 34.3 percent of those awaiting kidney transplantation, they receive only 24.8 percent of the cadaveric transplants and 14.3 percent of living donor transplants. Similarly, there are fewer transplants among Asians (3.7 percent cadaveric and 4.0 percent living donor) than would be expected from their representation on the waiting list (5.1 percent).

Retransplantation currently accounts for 17 percent of all kidney transplants, 15 percent of liver transplants, and 2 to 5 percent of all other organs transplanted. The number of patients being reenrolled on waiting lists has increased each year.

In 1994, more than 12,000 patients received allogeneic bone marrow transplants. When successful, bone marrow transplantation is curative therapy for immunodeficiency diseases, hematologic malignancies, aplastic anemia, and certain metabolic disorders. An additional 5,000 patients are potential candidates for marrow transplantation.

To prevent both graft rejection and graft-versus-host disease, it is important for donors and recipients to be human lymphocyte antigen (HLA) identical. Success rates vary among the different diseases treatable by bone marrow transplantation, but for low-risk patients, 2-year disease-free survival following unrelated bone marrow transplantation is 40 percent and drops to 19 percent for high-risk patients.

The Cooperative Clinical Trial in Transplantation, a multicenter clinical trial of new therapies for prolonging kidney graft survival, has finished enrollment in its donor-specific blood transfusion trial. The program has been successful in recruiting minority patients. Preliminary analysis has shown that this therapy shows efficacy in prolonging kidney graft survival, but the extent of this enhancement is not known. Patients will be followed for 10 years to determine if this therapy has a positive effect on long-term graft survival.

In FY 1994, NIAID established its first Cooperative Clinical Trial in Pediatric Transplantation at 35 medical centers to examine new treatments to prevent the rejection of transplanted kidneys in children. This cooperative research program will examine the causes of the lower patient and graft survival rates in children versus adults and the effects of immunosuppressive therapy on growth retardation. One of the major problems in transplantation is early rejection episodes, which predispose the grafts to eventual irreversible chronic rejection. The use of a monoclonal antibody, OKT37, before transplantation (i.e., induction therapy) is intended to stop the immune response to the organ before it begins. This phase III clinical trial is the proof of concept of a preliminary observation by the North American Pediatric Renal Cooperative Study that demonstrated a positive effect of antibody induction on graft survival. This result would allow children to retain their kidneys longer, possibly forever, and greatly improve their quality of life. In addition, this result could also be applied to other solid organs.

NIAID continues to chair and coordinate the National Institutes of Health’s (NIH) Transplantation Research Coordinating Committee. This committee fosters interactions not only among the various NIH institutes, centers, and divisions, but also between NIH and other Federal agencies. This open communication has enhanced the efficacy of federally funded projects in transplantation and has facilitated access to the various scientific and medical expertise needed for the planning and execution of these projects. On August 15, 1996, the committee hosted a meeting titled AEnhancing Organ Donation: State of the Art and Future Directions" to discuss the issues surrounding the lack of uniformity in how organ procurement organizations (OPO) approach increasing donations. The meeting included OPO directors and representatives from the General Accounting Office, Health Care Financing Administration, Health Resources and Services Administration, and the American Society of Transplant Physicians, as well as industry, congressional, and media representatives.