NIAID supports basic studies of virus structure, replication, gene regulation and evolution as well as studies in animals and humans that investigate the viral epidemiology, pathogenesis, and host immune response. This research program provides the foundation for the development of vaccines and antiviral therapies.

Respiratory infections are the major cause of acute illness in the U.S. NIAID supports the development and testing of new vaccines against virus-caused respiratory diseases such as influenza and respiratory syncytial and parainfluenza, which cause the majority of croup, bronchitis, and pneumonia in infants and children.

Viral hepatitis caused by hepatitis A, B, C, D, and E is another group of diseases with a major impact on health worldwide. In some parts of the world, hepatitis is the primary cause of liver cancer. Each year in the U.S., more than 600,000 new viral hepatitis infections occur which, when acute, can be debilitating and costly. Chronic disease resulting from infection with hepatitis B, C, and D is an even greater problem. Medical costs for chronic hepatitis are between $1 and $2 billion a year. NIAID-sponsored studies focus on virology, molecular biology, immunology, pathogenesis, development of antivirals, animal model development, natural history, vaccine development and clinical trials. Vaccines have now been licensed for hepatitis A and B.

Diarrheal diseases caused by viruses are particularly a problem among infants in developing countries. Experimental vaccines against rotaviruses--a major cause of infant diarrhea worldwide--have been extensively tested in children and infants. One vaccine developed in NIAID intramural laboratories is expected to be licensed for use in the U.S.

Although there have been reports of possible viral associations in chronic fatigue syndrome (CFS), no specific causative role for any virus has been demonstrated. In order to explore the possible causes of CFS, the institute has funded CFS Cooperative Research Centers to provide a multi-disciplinary approach to CFS research by conducting basic science and clinical investigations on CFS. NIAID also supports scientists who are studying the possible immune system dysfunction, reactivation of latent virus infections, exercise-induced fatigue in CFS patients, as well as other aspects of CFS pathophysiology, and its epidemiology.

Development of Antiviral Drugs. Because many drug sponsors do not have access to comprehensive antiviral screening facilities, NIAID has established screening facilities for the in vitro evaluation of an experimental compound’s activity against the human herpes viruses--herpes simplex virus (HSV) 1 and 2, varicella zoster virus, cytomegalovirus (CMV), and Epstein-Barr virus--and the respiratory viruses--influenza types A and B, respiratory syncytial virus, parainfluenza, measles, and adenovirus. This service is available to any scientist with a potential antiviral compound and an inability to test it. NIAID supports drug evaluation studies, preclinically in animal models of human viral infections and in human clinical trials. Institute-supported investigators participating in the Collaborative Antiviral Study Group are testing drugs for treating herpes encephalitis, neonatal herpes, hantavirus pulmonary syndrome, symptomatic congenital CMV infection, chronic hepatitis B virus infection, flu, and respiratory syncytial virus infection. Other investigators have evaluated interferons for human papilloma infections such as genital warts.

Bacterial Diseases. In the last decade, several bacterial diseases have emerged as new or recurring threats to the health of people in the U.S. and elsewhere, including Lyme disease and tuberculosis (TB).

Lyme disease, first recognized in the early 1980’s in this country, is caused by a bacterium transmitted to humans by certain ticks. It has emerged as a significant problem in the northeast coastal areas, among others. NIAID spearheads NIH studies on Lyme disease, supporting research focusing on pathogenesis, improved therapies, better diagnostic tests, and vaccines.

Tuberculosis, a serious disease once thought to have been conquered in the U.S., is reemerging in certain American cities. TB has a staggering impact worldwide, since one-third of the world’s population is infected with the TB bacterium. Although most people who are infected never develop active TB, those with weakened immune systems--especially those infected with HIV--are particularly vulnerable to active TB disease. Each year 8 million people world-wide develop active TB, and 3 million die.

With appropriate antibiotic therapy, TB usually can be cured. In recent years, however, drug-resistant cases of TB have increased dramatically. Particularly alarming is the increase in the number of persons with multidrug-resistant TB caused by bacterial strains resistant to two or more drugs. Even with treatment, the death rate for multidrug-resistant TB patients is 40 to 60 percent.

As the lead institute responsible for research on TB, NIAID supports basic research into the biology of TB, the development of new tools to diagnose TB, the development of new drugs or ways to deliver standard drugs, clinical trials of anti-TB therapies, and the development of vaccines to prevent it.

NIAID also funds research on leprosy, or Hansen’s disease, which is caused by a mycobacterium. Although treatable today, there are about 1.3 million leprosy patients requiring treatment worldwide, largely in subtropical climates. More than half a million cases are diagnosed each year. Research on atypical mycobacteria, which constitute a diverse and heterogeneous group of acid-fast bacilli that are widespread throughout the environment, is of increasing importance in light of the AIDS epidemic. These organisms rarely cause disease in healthy adults, however, they can cause serious opportunistic infections in people with impaired immune systems.

Cholera is a disease caused by the bacterium Vibrio cholerae. Infection results in severe, dehydrating diarrhea that is particularly dangerous to infants and small children. In 1991 cholera reappeared in the Western hemisphere for the first time in 100 years. The epidemic has spread as far north as Mexico and is a threat to travelers to Central and South America.

In 1992 a new strain of V. cholerae appeared in Asia and in the area of the Bay of Bengal. NIAID supports research aimed at understanding the pathogenesis of the disease, what constitutes protective immunity, and the development of effective vaccines.

Effective antimicrobial agents have significantly reduced the burden of bacterial infections, even though their usefulness is limited by increasing bacterial resistance to antibiotics and in those diseases with an onset and progression so rapid that effective treatment is difficult. NIAID supports the development and testing of bacterial vaccines for Hemophilus influenzae type b, Streptococcus pneumoniae, all causes of meningitis; pertussis (whooping cough); cholera; shigella; and typhoid fever.

Hospital-associated, or nosocomial, infections have emerged in recent years as a significant health problem and cause of increased morbidity and mortality. They directly contribute to rising health care costs. An estimated 2 million hospital-associated infections occur in the U.S. each year, at a cost of more than $3 billion.

Gram-negative sepsis following surgery or trauma remains the most serious threat to patients, with mortality rates ranging from 25 to 40 percent if sepsis occurs. NIAID supports studies on immune mechanisms--cellular and humoral--that protect healthy people against normal microbial flora commonly encountered every day. Another focus is the study of disturbances in resistance mechanisms in hospitalized or immunocompromised patients. Gram-negative bacteria from the gastrointestinal tract are the primary etiologic agents and many have become resistant to antibiotics.

Hospital acquisition and transmission of methicillin-resistant staphylococci, Candida, enterococci, and antibiotic-resistant gram-negative bacteria are important areas of investigation.

The interplay of bacterial toxins such as lipopolysaccharide and staphylococcal toxic shock toxin with host serum and cell components can result in fever, shock, and death. NIAID is investigating the underlying mechanisms of shock and its control and prevention.

Immediate aims are to improve means for diagnosing, treating, and controlling these diseases with the ultimate goal of disease prevention. For example, the U.S.-Japan Cooperative Medical Science Program, organized in 1965, provides an opportunity for American and Japanese scientists to cooperate in studying 10 disease-related areas of importance to the health of Asian people.

In September 1979, the International Collaboration in Infectious Diseases Research Program replaced the International Centers for Medical Research and Training which had been operational since 1960. Under the new program, research centers are established in tropical countries through multidisciplinary program project grants awarded to U.S. institutions. The program is designed to promote true collaboration and scientific exchange between U.S. scientists and their overseas counterparts. The program addresses infectious diseases of health importance to the host country. In 1991 NIAID established Tropical Medicine Research Centers to provide overseas facilities for the study of tropical diseases within endemic areas.

Other international activities include the NIAID-USAID Middle East Regional Cooperation Program, carried out through Jordan, Morocco, Lebanon, Tunisia, and Israel, to study leishmaniasis and hydatid disease. NIAID also coordinates studies on the immunology of infectious diseases as part of the Indo-U.S. Science and Technology Initiative.

Basic research is supported in 1) immuno-biology and immunochemistry and 2) immunogenetics and transplantation immunology. Clinical research is supported in asthma and allergic diseases, and immunologic diseases and immunopathology. NIAID's approach integrates the basic science disciplines with relevant clinical specialties.

Basic Immunology. The biology and chemistry of the immune system and its products are the concerns of this program area. Immunobiologic studies focus on the origin, maturation, and interactions of the immune system's major cells, lymphokines, and other substances produced by theses and other cells that mediate immune reactions. Studies include the mechanisms responsible for the induction and regulation of the immune response. Immunochemical research encompasses the delineation of the chemical structure and function of antigens and antibodies; the chemical basis of immunologic specificity; the regulation of immunoglobulin synthesis; and the mechanisms of antigen-antibody reaction.

Research projects in this area are designed to:

• Elucidate the critical immunologic functions of T cell receptors, cell-adhesion molecules, and cytokines and their receptors in various systems in the human body and in laboratory animals.
• Isolate and characterize human stem cells;
• Participate in the formulation of a repository of cell lines and gene probes for use in the study of mucosal immunity and digestive diseases;
• Elucidate the chemical nature and structure of small organic molecules that generate allergic and hypersensitive responses; and
• Investigate the interactions of selected immunotoxicants with the secretory immune subsystems of the gut and respiratory tract.

• Clarify the organization and mechanisms of expression of the genes on which immune function depends;
• Characterize protein products of genes, including histocompatibility antigens;
• Determine how these gene products condition the response to foreign antigens; and
• Develop regimens to modulate the immune response and facilitate engraftment of transplanted organs and tissues.

By supporting the acquisition, characterization and distribution of tissue typing reagents and the evaluation and improvement of tissue typing methodologies, the program facilitates the matching of donors and recipients for transplants. It also supports studies on the relationship of the human major histocompatibility complex (MHC) HLA antigens to disease susceptibility.

Research projects in this area are designed to:

• Investigate the mechanisms and innovative use of immunosuppressive drugs;
• Develop new monoclonal antibodies directed against specific cells to prevent graft rejection;
• Further develop reagents for precise typing of MHC or tissue matching; and
• Delineate the development of the fetal and adult immune response, using in vitro systems.

Some of these reagents are available for use in workshops or similar large-scale studies.

The institute also is a primary source of standard reagents for distribution and analyses for basic immunogenetic studies of murine transplantation antigens.

Transplantation. Program projects in transplantation immunology, located at major transplant centers, are currently funded by NIAID to facilitate the rapid translation of basic immunologic discoveries into clinical use. The centers carry out basic and clinical research pertinent to mechanisms of rejection, organ availability and preservation, and management of rejection.

National Cooperative Clinical Trial in Transplantation. NIAID established this trial to expedite the evaluation of new treatment modalities to prevent kidney graft rejection. Multicenter clinical trials to assess thepotential efficacy of various therapies are conducted at eight kidney transplant units throughout the U.S.

Asthma, Allergy and Inflammation. More than 50 million Americans suffer from allergic diseases including asthma. NIAID supports studies encompassing the cause, pathogenesis, diagnosis, prevention, and treatment of allergic diseases. Various types of allergic problems under investigation include: immediate type hypersensitivity and its disorders, including asthma, allergic rhinitis, atopic dermatitis, urticaria and angioedema; allergic reactions and disorders caused by insect bites and stings, foods, airborne allergens, and infectious agents; manifestations of delayed hypersensitivity and contact dermatitis; and the mechanisms of drug reactions and chemical sensitization. Studies also include structure of the antibodies, particularly IgE, and the chemical mediators released by the interaction of antigen and antibody with target cells; the isolation and chemical characterization of the active fractions of allergenic agents; and the therapy and prevention of allergic disorders and hypersensitivity reactions by immunotherapy with specific antigens or drugs.

Asthma, Allergic and Immunologic Disease Cooperative Research Centers. A network of cooperative research centers represents an effort to integrate the basic concepts of immunology, genetics, biochemistry, and pharmacology into clinical investigations of patients with asthma, allergic and immunologic diseases. The program encourages collaboration between basic and clinical scientists, provides a research environment for such interactions, and implements clinical application of adequately tested research findings and procedures. It is believed that this will lead to an understanding of the pathophysiologic, biochemical, and immunologic mechanisms of these disorders.

National Cooperative Inner-City Asthma Study. NIAID established this study to assess the factors contributing to the increased morbidity and mortality from asthma among children residing in urban environments, and to develop and evaluate a comprehensive therapeutic, educational, and environmental intervention program designed around those contributing factors. Seven sites in six cities nationwide are participating in this cooperative study.

Clinical Immunology. Investigations of underlying mechanisms of disease and applications of basic knowledge to the cause, prevention, and management of immunologic disorders are approached from either of two disciplines--clinical immunology or immunopathology. Studies of clinical immunology involve acquired and inherited diseases associated with dysfunctions of the immune system, whereas the immunopathology studies encompass genetics, cytology, biochemistry, pathology, and pharmacology of the immune system.

Areas under investigation include:

• Immune deficiency diseases arising from primary defects in development or maturation of the immune responses;
• acquired immune deficiency disorders excluding AIDS;
• clinical manifestations mediated by products of lymphocytes;
• diseases associated with immune complexes and autoimmune phenomena; and
• immunotherapy of disease process, including the use of immunopotentiating and immunoregulatory substances.

DAIT supports program projects in mechanisms of immunologic diseases and autoimmunity aimed at increasing the understanding of pathophysiologic processes of immune-mediated diseases and the development of improved methods of diagnosis, treatment and prevention of disorders of the immune system.

DAIDS accomplishes this mission by planning, implementing, and evaluating programs in:

• fundamental basic and clinical research,
• discovery and development of therapies for HIV infection and its complications,
• discovery and development of vaccines and other preventive interventions, and
• training of researchers in these activities.

In accord with this mission, the division's efforts are organized around five broad scientific areas: 1) pathogenesis, 2) epidemiology and natural history, 3) therapeutics research and development, 4) vaccine and prevention research and development, and 5) pediatric disease.

HIV Pathogenesis. Research on the pathogenesis of HIV infection will advance the understanding of the biological causes of HIV-related disease and serve as a foundation for advancing treatment and prevention.

Investigator-initiated research and the traditional research grant are the foundation of the division's activity in this area. Important research gaps are identified by division staff in concert with investigators and advisory committees.

Other key NIAID resources for the study of pathogenesis include:

• longitudinal epidemiological studies of cohorts of individuals infected with, or at risk of infection with, HIV, and serially collected specimens stored in an DAIDS-supported repository;
• animal model research and development projects;
• the NIAID AIDS Reference and Reagent Repository, through which DAIDS acquires and distributes essential research reagents to scientists around the world; and
• the Centers For AIDS Research (CFARS), designed to support coordinated scientific and administrative activities that enhance the capacity for collaboration between basic and clinical research.

Epidemiology and Natural History. The division's goals in the area of epidemiology and natural history are to foster population-based research that will advance the understanding of the biology and clinical course of HIV infection and serve as a foundation for advancing treatment and prevention.

The division oversees several large longitudinal cohort studies that conduct multidisciplinary research involving specific populations of individuals infected with or at significant risk of infection with HIV. These include:

• Multicenter AIDS Cohort Study,
• San Francisco Men's Health Study, and
• Women's Inter-Agency HIV Study.

Vaccine and Prevention Research and Development. Development and testing of vaccines and other biomedical interventions such as drugs and microbicides to prevent HIV disease is a key role of DAIDS-funded research.

NIAID's efforts in vaccine research and development are built on a strong foundation of investigator-initiated research in basic virology, immunology, and microbiology. In addition, the division uses a number of specific applied resources to advance its objectives. These include:

• National Cooperative Vaccine Development Groups (NCVDGs), in which research teams from industry, academia, and government collaborate to develop and test novel experimental HIV vaccine concepts;
• SIV Vaccine Evaluation Units, which conduct standardized and directly comparable evaluations of various SIV vaccine candidates;
• Chimpanzee Unit, which is used to prepare stocks of virus for use in chimpanzees and to evaluate candidate vaccine concepts and products in chimpanzees;
• the AIDS Vaccine Evaluation Group (AVEG), which conducts phase I and II clinical trials of candidate HIV vaccines;
• central immunology laboratory facilities in support of the activities of the NCVDGs, the SIV-VEUs, the Chimpanzee Unit, and the AVEG;
• HIV Variation Project, which investigates the rate and magnitude of genetic variation in HIV and related retroviruses and explores the impact of this variation on strategies to develop HIV vaccines;
• Cooperative Group for Investigations of AIDS Vaccine Adjuvants, which supports investigator-initiated research into the mechanisms of adjuvant action, develops new adjuvant formulations to stimulate immune responses and generate long-lasting immunity and immunological memory, and evaluates vaccine-adjuvant combinations in relevant animal models;
• HIV Network for Prevention Trials (HIVNET), which consists of both domestic and international sites that conduct trials of HIV vaccines and other prevention strategies.

  Researchers at HIVNET sites also study cohorts of individuals at high risk for HIV infection to prepare conducting vaccine efficacy trials within these populations.

• Collaborative Mucosal Immunity Groups (CMIG), which characterize the immune response to HIV in both infected individuals and uninfected vaccinated people and primates.

Therapeutics Research and Development. The division’s goal in therapeutics is to foster the discovery and development of interventions that will improve the quality and duration of life of HIV-infected individuals.

NIAID devotes substantial resources to the discovery stage of therapeutics research, attempting to focus resources on areas of promise that are receiving insufficient attention from the private sector. The effort begins with a strong commitment to basic research in microbiology and pathogenesis. Upon this are built programs of targeted drug discovery with the National Cooperative Drug Discovery Groups (NCDDGs) for HIV and opportunistic infections (OIs) at the center. These consortia of academia, industry, and government investigators work collaboratively on focused “gap” areas of targeted drug discovery. Small portfolios of highly applied traditional investigator-initiated research round out this effort.

NIAID’s preclinical development resources are limited in scope to those necessary to ensure that the national effort has the capability to carry out specific rate-limiting developmental steps involving selected highly promising candidate agents that lack a private sponsor with sufficient resources or commitment. These “gap-filling” resources include capabilities for 1) chemical resynthesis; 2) analytical chemistry and quality control; 3) dosage form development and manufacturing; 4) small and large animal toxicology; and 5) in vitro screening and animal model efficacy studies.

In addition, the Special Program for Innovative Research on AIDS Treatment (SPIRAT) fosters coordinated and interdependent basic and clinical research between current HIV pathobiology and clinical evaluation of novel therapeutic strategies.

NIAID conducts clinical trials of new therapeutics in three networks:

• Adult AIDS Clinical Trials Group--a large, multicenter clinical trials network;
• Terry Beirn Community Programs for Clinical Research on AIDS--designed to address questions of importance to primary care clinicians and extend opportunity for participation in trials to persons underrepresented in HIV research; and
• Division of AIDS Treatment Research Initiative--a program designed to rapidly address critical questions or innovative treatment approaches.

Pediatric Disease. DAIDS is working to identify and support the development of improved interventions to prevent and treat HIV infection and its sequelae in infants, children, and adolescents. DAIDS’ goals in pediatric disease include: 1) preventing perinatal HIV transmission to infants and HIV transmission to adolescents and children; 2) developing technology for the early identification and diagnosis of HIV-infected infants; and 3) developing and optimizing therapies for HIV and its sequelae in infants, children, and adolescents.

Specific resources related to pediatric disease include:

• Women and Infants Transmission Study, a longitudinal cohort study of infected women and their children;
• Pediatric AIDS Clinical Trials Group; and
• investigator-initiated research, both solicited and unsolicited, addressing issues of pediatric disease.

The scope of laboratory investigations includes the disciplines of virology, parasitology, mycology, microbiology, biochemistry, immunology, immunopathology and immunogenetics. Additionally, the DIR supports a 52-bed inpatient service and an outpatient facility located in the Clinical Center on the NIH campus. Patients with a variety of diseases under study, including AIDS, vasculitis, immunodeficiencies, host defense defects, unusual fungal infections, asthma, allergies, various parasitic diseases and disorders of inflammation, are seen. Frequently these patients participate in new and exciting treatment or diagnostic procedures derived from ongoing laboratory research efforts.

Successful vaccines or therapies for infectious diseases derive from a myriad of research activities on the disease agent as well as interactions of the agent with the host. The human immunodeficiency virus associated with AIDS is a major challenge to DIR scientists and physicians. The development of suitable laboratory animal models is critical to developing therapeutic strategies and vaccines for AIDS.

DIR scientists are studying the immunopathogenesis of HIV infection as well as the immune response to the virus. Cytokines have been shown to induce the expression of HIV in latently or chronically infected cell lines,thus providing tools for understanding the mechanisms of the insidious progression of immunosuppression in HIV-infected individuals.

In addition, NIAID researchers are exploring the many components of HIV disease, including phases of immune system activation and suppression. In studying the dissemination of HIV to lymphoid tissues in the body such as the lymph nodes and spleen, the investigators have found that HIV is active within these tissues from the earliest stages of HIV infection. This finding provides a scientific rationale for early treatment when safer and more effective antiretroviral drugs become available. DIR investigators have conducted intensive studies of antiretroviral and immuno-modulator therapies. Clinical trials of a number of therapies, including use of IL-2 to maintain CD4 levels, are under way.

NIAID intramural scientists are working to develop and test vaccines against a number of infectious agents such as viruses causing AIDS, dengue fever, diarrhea in infants, and pneumonia and croup in infants and young children. Bacterial agents that cause sexually transmitted diseases such as chlamydia and gonorrhea, and Lyme disease are under active investigation. Approaches to the development of a vaccine against malaria are being explored. Promising new vaccine candidates are tested in the clinical setting for safety, immunogenicity, and if warranted, efficacy.

Basic immunologic studies are aimed at defining the components and mechanisms of action of the humoral and cellular responses. Receptors on T lymphocytes and peptides linked to the surface of antigen presenting cells are being defined. Information derived from these studies may allow the design of peptides that can inhibit specific immune responses and may have great importance in controlling the rejection associated with transplantation.

DIR researchers are carrying out intensive studies of the role of newly discovered cytokines in T-cell differentiation. Researchers have found that interleukin 12 (IL-12) plays a pivotal role in the induction of T-cell responses, which are important for the control of intracellular infections.

B lymphocytes, critical components of the immune response and responsible for antibody responses, are being dissected for studies of structure and function. Among the studies being conducted are those related to the control of B-cell immunoglobulin class switching. It has been shown, for instance, that IL-4 and INF-gamma reciprocally regulate IgG1 and IgE responses in mouse systems. In addition, the role of TGF-beta in IgA class-switching has been clarified. These studies are important in the design of future vaccines that can enhance the production of certain forms of antibody.

Inflammation is an important aspect of immunity. One of the important mediators of inflammation is a series of nine proteins called the complement system. NIAID scientists identified a new protein present in large concentrations in plasma of humans. The new protein binds to the fourth protein of the complement cascade where it acts as an inhibitor of this important inflammation-producing system. The inhibitor also interacts with the kinin-generating and coagulation systems. Certain patients with unusual swelling disorders have an abnormality in the degradation of this protein, and thus the protein may be very important in certain swelling disorders.

The first evidence that an immunodeficiency can be treated with a naturally occurring product of lymphocytes was recently demonstrated by DIR scientists. Chronic granulomatous disease of childhood (CGD), a disease in which there is a defect in the ability of the scavenger cells of the immune system to produce hydrogen peroxide, renders the patient susceptible to certain infectious agents. A multicenter clinical trial of interferon gammain patients with CGD followed in vitro studies which demonstrated the effectiveness of interferon gamma in correcting the defect in phagocytes from these patients. Interferon gamma was shown to significantly reduce the number of serious infections in CGD patients. These studies led to FDA approval of this drug for use in CGD.

Studies of the immune response to the causative agent of leishmaniasis have demonstrated that immunity to the parasite is not only to a specific antigen, but also to a certain immune cell. DIR scientists have shown that the outcome of leishmaniasis depends on whether the animal develops a TH1 response with T cells that produce IL-2 and IFN-gamma, or a TH2 response with T cells that produce IL-4 and IL-5. In the former case, granulomas develop that wall off and kill leishmania in the latter case, the infection is disseminated.

Studies of allergy are carried out by investigators working in basic immunology laboratories as well as by clinical and laboratory investigators working within the Asthma and Allergic Diseases Center. One effort has been the study of IgE antibody which mediates allergic responses by causing mast cells to release mediators of allergic responses. IL-4, produced by T cells, is essential for production of IgE in mice. Administration of IL-4 to mice prevented increases in IgE antibodies normally observed in immune responses to certain antigens. In other studies, DIR scientists have developed a “knockout” mouse that lacks receptors for IgE antibodies on the surface of mast cells. These mice will facilitate a better understanding of the role of IgE responses in the production of allergic symptoms.

Studies of the mechanisms of allergies have emphasized work on mast cells. Mast cells are the central cells of allergic responses because when activated by an allergen and IgE they release the mediators of allergy. New techniques have been developed in order to grow human mast cells in culture, an advancement that will enable more detailed investigations into their biology. An improved approach to the treatment of asthma has been devised by DIR researchers. The concept is based upon separating bronchodilators from agents that act to reverse specific processes in the pathogenesis of asthma. Specifically, patients are placed on symptomatic therapy in order to permit the more specific therapy to act. Inhaled cromolyn, systemic corticosteroids and immunotherapy are employed as specific agents while beta adrenergic agonists, theophylline, and atropine are symptomatic agents. This approach is gaining increased acceptance and should improve long-term treatment of asthma.