NIAID initiatives in allergy research

The Journal of

ALLERGY and

CLINICAL VOLUME

IMMUNOLOGY

49

NUMBER 6

NIAID initiatives in allergy research Dorland Bethesda,

J. Davis, Md.

M.D.*

Allergic diseases manifest their toll in morbidity and its conseqzlences rather than in death rates. About 31 million Americans each year suffer from some form of allergio disease, inolnding 8.6 million from asthma. As a cause of limitation of aotivity in persons Under 45, asthma-hay fever is second OT third only to impairments of the back and mental conditions. It is also the leading oazlse of limitation of activity under the age of 17. l’he NIAID supports $77 project grants, including 49 for CliniCal StudieS, 47 for research training grants, and 69 for fellowships in the general area of immwnology and allergy. A new program supports 7 allergio disease centers where high research competence is coupled with clinical skills in an outpatient setting for investigation of diseases of the time&ate hypersensitizrity type. It seems clear that today there is no field of soientifio medicine that has greater opportunities to bring new lcnowledge to the relief of patients and prevention to their suflering than that of allergic diseases.

I am particularly pleased to talk to you at this time because I am sure there are no greater opportunities in scientific medicine today than in the field of allergic disease. We are on a threshold of new advances in the clinical management and prevention of maladies that have afflicted patients and frustrated physicians since the beginning of medical practice. The allergic diseases are notable primarily for causing disability and disrupting life patterns in child development and family life. They do not cause many deaths. Asthma, the only one of the group with a significant mortality rate, accounts for only about 4,000 deaths per year. Anaphylactic deaths are tragic and dramatic but number only several hundred a year in the United States. Compared to the death toll of heart disease, cancer, and infectious Presented at the Annual meeting of the American California, February 7, 1972. Received for publication March 10, 1972. Reprint requests to: Dr. Davis, Bldg. 31, Room 7A52, Md. 20014. *Director, National Institute of Allergy and Infectious

Academy

National

of

Allergy,

Institutes

San

Francisco,

of Health,

Bethesda,

Diseases. Vol.

49, No.

6, pp. 3&T’-368

J. ALLERGY

324

Davis

TABLE

I. Asthma

IMMUNOL. JUNE 1972

prevalence Rate Name

Current

National Health Interview Survey-1967 National Health Examination Survey-1962 Maryland Study (Rhyne)-1963 Tecumseh, Michigan, Community Health Study (Broder)-1962-1965 Selected College Studies (Maternowski, Hagy, Sherry, Van Arsdel)-1956-1965

TABLE (Rates

CLIN.

II. United States Prevalence per 100 noninstitutionalized

Condition

Asthma Hay fever without asthma Other allergic disorders Chronic sinusitis Chronic bronchitis

per

100

Population segment

Cumulative

3.0

-

All

3.4

5.4

18-79

3.0 3.8

6.9 6.6

6-11 yr. All ages

-

of chronic population]

Total

Average,

respiratory

4.8

conditions,

Under

45 yr.

College

FY 1966

ages yr.

age,

to

17-22

1967

45 yr. ond over

2.9 ;:i 2.8 8.6 2.1

2 EJ 6:s 1.8

1K 2:9

respiratory disease, asthma and other allergic diseases may seem a minor health problem. But death rates are not a good measure of the impact of allergic diseases on the nation’s health. We must develop better ways to assess their toll in terms of morbidity and its consequences. Several careful though limited studies of the prevalence of asthma are shown in Table I. Mr. Joseph Schachter of our Institute has selected 4 individual studies and pooled data from 4 college studies.l-7 These data indicate similar prevalence rates as determined in different studies and at different ages. We can estimate that about 4 per cent of the American people are presently suffering from asthma and about 7 per cent have suffered at some time. Translated to national figures, it means that about 8.6 million Americans are handicapped by asthma and about 14 million either are or have been afflicted. Mr. Schachter has estimated that some 31 million Americans suffer from some form of allergic disease of the immediate hypersensitivity type. These estimates do not include cellular immunity disorders. Other data help to define the impact of allergic diseases, particularly for school and working ages. Unpublished data from the National Center for Health Statistics for 1966 to 1967 compare prevalence rates for 5 chronic respiratory conditions (Table II) .I In contrast to many disease conditions that show a precipitous rise over age 45, allergic disorders exert an equal impact on those under 45. Indeed, data from the National Health Survey in 1966 to 1967 show that as a cause of limitation of activity in persons under 45, asthma-hay fever is, depending on income, second or third only to impairments of back and spine

NlAlD initiatives 325

VOLUME 49 NUMBER 6

TABLE III. impact

of asthma-hay

fever

22 million (8.6 85 million 33 million 5 million 7 million 27 million

TABLE

IV. Hospitalization

Age Total Under 15 yr, 15-44 yr. 45-64 yr. 65 yr. and over

data

for

Americans currently afflicted million have asthma alone)$ days restricted activity’ days in bed’ days lost from work’ days lost from school’ patient visits to physician+’

asthma-hay Number of patient discharges

fever,

1968 Average length of stay (days1

Estimated hospitalization cost ($55.80 per day)

134,000

8.3

62,061,OOO

32,000 37,000 38,000 27,000

6.6 6.2 1;::

11,785,OOO 12,801,OOO 16,751,OOO 20,339,ooo

and mental and nervous conditions.e Perhaps even more significant-asthma-hay fever was the leading cause of limitation of activity among a large number of persons under the age of 17. The National Health Interview Survey also det.ermined that in 1967 a daily average of 25,400 persons aged 17 and over were absent from work because of chronic allergic conditions and that the total number of work loss days was 6,242,OOO. Table III shows several other measures of the burden of allergic diseases.gl L lo Table IV shows the impact in terms of hospitalization. In 1968, the most recent data year, there were 134,000 patient discharges with a diagnosis of asthma-hay fever.l These involved an average length of stay of 8.3 days and an estimated hospitalization cost totaling about 62 million dollars.ll Vance and Taylor12 studied the financial .burden of childhood asthma in 21 selected families in southern California and found the cost ranged from 2 to 30 per cent of the family income. I need not tell this audience o-f the demand made on physicians by the conscientious care of allergic patients. The National Disease and Therapeutic Index reports that asthma alone accounts for one third as many patient office visits as does essential hypertension, the leading diagnosis, and about half as many visits as does diabetes.5 These are all inadequate appraisals of the impact of allergic diseases, and in NIAID we plan to develop more precise data on patterns of patient visits as well as information on the economic burden. What is the National Institute of Allergy and Infectious Diseases doing about these difficult problems? Since its establishment in 1955, the NIAID has steadily increased the proportion of funds and effort going into immunologic and allergic disease research. At an early stage we directed attention to building a stronger science base both in university settings by project and training grants, and in our own laboratories at Bethesda. This has coincided with and assisted a remarkable increase in fruitful research on the understanding of immunologic mechanisms coupled with the development of innovative techniques. Further-

326

Davis

i. ALLERGY CLIN.

IMMUNOL. JUNE 1972

more, the discipline of immunology has att.racted a. host of ima.ginative young investigators who are now seeded throughout the nation as ttxchers and clinicians well grounded in nmclcrn research techniques. The MAID purposes to continue and, if possible, tu accelerate its support of research and research training in the broad field of immunology. In addition! we believe we have not only an opportunity but an obligation to encourage sound clinical investigations directed at disease in the patient. It is time that the whole array of new knowledge and techniques lx brought to bear on specific clinical disorders which afflict* man. Before I mention the now initiatircs that, h:lAlT) will ullclrrtake, let MC review the present. grant support for which Dr. Maurice Landy has stewardship. Currently, the Institute supports 2177 projects grants cwsting $14,100,000 in the general area of immunology. This is nearly ant -fourth of the total Institate grant funds. O-f these, 59 grants laosting $2,8X,000 relate direc%ly to clinical disease. Forty-scvcn research training grant,s in major research centers provide opportunities in both laboratory and clinical research for trainees. Fellowships and Research (Yarecr I)evelopment~ Awards provide funds for 69 scientists to further develop t,heir investigative ahilities. Intramurally, the NIALD (annducts active research ill the l,aborat,or;v of l.mrnunology organized first by l)r. ,lulcs Freund. Other laboratories of the SIA II) art’ also conccrnc:d m&h clinical and laboratory studies of immunologic diseascl. of Course other Institutes of NIII support work in immunology and rheumat~ology. A new program, tht> ,Ulergic: Disease (:rl\ters, is espe&lly designed to support the scientific applicantion of new laboratory findings to the treatment and prevention of allergic disease. It, is funded from a spr&l budget item which gives authority to support clinical care for rtsealach patients and does not compete with research project grants or training money. I’LIS~May, with approval from the National Sdvisory Allergy and Infectious Diseases Council, we awarded competitive grants to 7 institutions that hat1 recognized high research competence. primarily in immedialc hypersensitivity and also clinical facilities for out patients. These institutions arc: ‘1’li~ Scripps C’liilic ai~d Research Foundation, I:niv-c~rsity, St. lionis; Kational Jewish Iiniversity of Risconsiu; Washington Hospital, and C%iIdren’s Asthma, I~rsw rch Jnstitute and Hospital, L)enver; Johns Hopkins lTnircrsit,y, and Wobe~t B. Brigham Hospital, Boston. We espect to expand this number in l!) ‘2 1 wit,11 t.he aid OF earmarked funds atltleroct’(l i’or KlX J1). I :11x1eert,a,in that the special trstimon) by several members of the Amrric*an Academy of Allergy was very helpful to the Appropriations Committees of tllc! (‘ongr~ss. The NIAID wnduct,s other act,ivit,ics designctl t,o expedite the translation of new resea.rch knowledge into improvrct patient care. For instance, for a number of years we have funded contracts to provide purified ragweed pollen antigen E reagent.s. Two reagents arr now ready and announcements are being made of bhcir availability in Iimitctl amounts for investigational purposes. Soon we will fund new contracts for production of additional ragweed reagents, including antigen Ra3, K, and possibly ot,hers.

VOLUME 49 NUMBER 6

NIAID

initiatives

327

The NIAID has also awarded a contract to the Allergy Foundation of America to develop diagnostic criteria for asthma and allergic rhinitis, a need long felt by clinical investigators for evaluation and comparability studies. Many of you will have a chance to participate in this endeavor. The NIAID is proposing to establish an information network for informal and rapid scientist-to-scientist communication on immediate hypersensitivity. If established, it would be called the Immediate Hypersensitivity Scientific Memorandum and will contain brief notes and preliminary data sent on a bimonthly basis to active investigators who make a contribution at least once a year. It is really intended as an extension of the informal verbal discussions that take place at meetings such as this. Similar scientific memoranda are already functioning well in the fields of hepatitis, interferon, and leprosy. Other communications projects have been the Science Writers Seminars jointly sponsored by the American Academy of Allergy and NIAID. We had a very successful seminar here last Friday, one in May in Atlantic City, and another a year ago in Baltimore. These provided opportunities for science writers of the press to hear the latest reports from active researchers. I mention briefly a hope that we have of being able to suppport an accelerated program in clinical immunology. Such a program would support development and evaluation of diagnostic procedures and therapy needed in hospital practice for diseases such as the rheumatoid diseases, SLE, and immune deficiency states. In closing let me say again that I believe no field of scientific medicine today has greater opportunities to bring new knowledge to the relief of patients and prevention of their suffering. Allergic diseases are a major cause of chronic illness and limited activity, particularly in the young. There are no fewer than 23 special hospitals and 7 summer camps for asthmatic children alone in the United States and Canada which are manned by skilled physicians and dedicated nurses. I3 Let us hope that the time is not far off when such institutions will no longer be needed and will go the way of tuberculosis sanitoria and communicable disease wards, after the advent of specific antibiotic therapy and effective immunization. As physician-scientists, we aim for no less. REFERENCES 1 National Center for Health Statistics, United States Public Health Service. Unpublished data. 2 Rhyne, M. B., Nathanson, and C. A., Mellits, E.: Determination of prevalence and special needs of children with bronchial asthma or atopic dermatitis, final report to United States Department of Health, Education, and Welfare, Childrens Bureau, Project NOS. 212 and H-188(R), April, 1971. 3 Tecumseh Community Health Study, IJniversity of Michigan School of Public Health. Unpublished data. 4 Maternowski, C. J., and Mathews, K. P.: The prevalence of ragweed pollinosis in foreign and native students at a midwestern university and its implications concerning methods for determining the inheritance of atopy, J. ALLERGY 33: 130, 1962. 6 Hagy, G. W., and Settipane, 0. A.: The frequency of allergies and positive skin test among college students, J. ALLERGY 37: 107, 1966. 6 Sherry, M. N., and Scott, R. B.: Prevalence of allergic diseases in freshman college students: A survey based on a predominantly Negro population, Ann. Allergy 26: 335, 1968. 7 Van Arsdel, P. P., Jr., and Motlusky, A. 0.: Frequency and hereditability of asthma and allergic rhinitis in college students, Acta Genet. Med. Gemellol. (Roma) 9: 101, 1959.

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IMMUNOL. JUNE 1972

8 National Center for Health Statistics: Chronic conditions and limitations of activity and mobility, United States, July, l$J6B to June, 1967, Vital and Ilealth Statistics, United States Public Health Service, Publication No. 1000, Series 10, No. 61, January. 1971. 9 National Institute of Allergy and infectious Diseases, National Institutes of lfenlth. Unpublished estimates prepared .Janunry, 1971. The private practice asthma market, 31a)-j 10 Lea Research Group, Ambler, Pennsylvania: 1970. 11 Figures on expense per pat,ien t day, Section on Hospit,:\ Stntistics---Statistical Tnl)le~, .r. Am. Hosp. Assoc. 45: (Part 2). 462, 1971. 12 Vance, 1’. J., and Taylor, W. F.: The flnaucial cost of chronic childhood asthma, Ann. Allergy 29: X%i, 1971. dcatlern~ of Pediatrics, 13 Institutions and Camps for 22sthmatie (!l~ildren, 1971, hnmrican Evanston. 111.