The Selection of Patients for X-ray Examinations: Chest X-Ray Screening Examinations US. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service - Food and Drug Administration ''PUBLIC HEALTH LIBRARY / BERKELEY | LIBRARY USUIVERSITY cnurontta 7 NCDRH PUBLICATIONS - RADIOLOGICAL HEALTH Publications of the National Center for Devices and Radiological Health (NCDRH) are available aper copies from either the U.S. Government Printing Office (GPO) or the National Technical formation Service as indicated by the GPO or PB prefix, respectively, on the ordering number. Publications are also available in microfiche from NTIS at $4.50 per copy. To receive all NCDRH reports in microfiche, at $1.00 each, you may establish a deposit account with NTIS and request automatic distribution of "FDA/HFZ" reports under the "Selected Research in Microfiche" prog- gram. Those publications without GPO or PB numbers are available only from National Center for Devices and Radiological Health. Addresses for ordering are: Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402; National Technical Information Service, Springfield, VA 22161 (outside North America, prices are double those listed); and National Center for Devices and Radiological Health, Food and Drug Administration (HF X-28), 5600 Fishers Lane, Rockville, MD 20857. All prices are subject to change. FDA 81-8151 A Feasibility Study of the Biological Effects of Fallout on People in Utah, Nevada, and Arizona (PB 81-187692, $7.00). FDA 81-8152 Annual Report of the Division of Biological Effects, Bureau of Radiological Health - Fiscal Year 1979 (PB 81-187155, $13.00). FDA 81-8153 on Evaluation of Radiation Emission from Video Display Terminals (PB 81-198483, 10.00). FDA 81-8155 A Practitioner's Guide to the Diagnostic X-Ray Equipment Standard (GPO 017-015- 00185-7, $2.50). FDA 81-8156 Symposium on Biological Effects and Measurement of Light Sources (GPO 017-015- 00191-1, $7.50) (PB 81-214223, mf only). FDA 81-8157 An Intercomparison of Nuclear Medicine, Ultrasonography, and Computed Tomography in the Diagnosis of Liver Disease: A Retrospective Study (PB 81- 199044, $8.50). FDA 81-8158 Background Material for the Development of the Food and Drug Administration's soos on Thyroid-Blocking with Potassium Iodide (PB 81-205361, 8.50). FDA 81-8161 By Routine Compliance Testing for Diagnostic X-Ray Systems (PB 81-201501, 17.50). FDA 81-8162 Handbook of Computed Tomography -X-Ray Spectra (PB 81-295890, $13.00). FDA 81-8163 Airborne Ultrasound: Measurement and Possible Adverse Effects (GPO 017-015- 00193-8, $3.00) (PB 81-240459, mf only). FDA 81-8164 Calculation Programs for Routine Compliance Testing of Diagnostic X-Ray Systems (PB 81-200503, $10.00). . FDA 81-8166 Third International Radiopharmaceutical Dosimetry Symposium (October 1980) (GPO 017-015-00194-6, $12.00) (PB 81-233090, mf only). FDA 81-8169 Pilot Study of Social Security Administration Disability Claims (SSADC), by Selected Diagnosis and Qualified Radiation Exposure (PB 81-246761, $11.50). FDA 81-8170 Effects of Ionizing Radiation on the Developing Embryo and Fetus: A Review (GPO 017-01 5-00198-9, $6.50) (PB 82-115379, mf only). FDA 81-8171 Self-Assessment and Competency Assurance Education in Diagnostic Radiologic SEO Final Report (September 30, 1977 to April 30, 1980) (PB 81-237448, 8.50). FDA 81-8172 Plain Skull Film Radiography in the Management of Head Trauma: An Overview (PB 82-120130, $8.50). FDA 81-8173 Pre-Employment Low Back X Rays: An Overview (PB 82-122979, $7.00). FDA 81-8174 The Selection of Patients for X-Ray Examinations: The Pelvimetry Examination (brochure). FDA 81-8175 Source Book of Educational Materials for Nuclear Medicine (GPO 017-015-00199- 7, $6.50) (PB 82-116153, mf only). FDA 81-8176 Administratively Required Dental Radiographs (GPO 017-015-00201-2, $3.25) (PB 82-117581, mf only). FDA 81-8177 Emission Computed Tomography: The Single Photon Approach (GPO 017-015- 00200-4, $8.50). (Continued on inside back cover) '' s 5 hi be, HHS Publication (FDA) 83-8204 1 SEF The Selection of Patients for X-ray Examinations: Chest X-Ray Screening Examinations WHO Collaborating Centers for: © Standardization of Protection Against Nonionizing Radiations ® Training and General Tasks in Radiation Medicine © Nuclear Medicine August 1983 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Food and Drug Administration National Center for Devices and Radiological Health Rockville, Maryland 20857 ''pp FHERTTE The opinions and statements contained in this report do not necessarily represent the views or the stated policy of the World Health Organization. ii ''KC yz7 KeS44 CUBE FOREWORD In October 1982, the Food and Drug Administration established the National Center for Devices and Radiological Health (NCDRH) by merging the Bureau of Medical Devices and the Bureau of Radiological Health. The Center develops and implements national programs to protect the public health in the fields of medical devices and radiological health. These programs are intended to assure the safety, effectiveness and proper labeling of medical devices, to control unnecessary human exposure to potentially hazardous ionizing and nonionizing radiation, and to ensure the safe, efficacious use of such radiation. The Center publishes the results of its work in scientific journals and in its own technical reports. These reports provide a mechanism for disseminating results of NCDRH and contractor projects. They are sold by the Government Printing Office and/or the National Technical Information Service. Also, NCDRH technical reports in radiological health are made available to the World Health Organization under a memorandum of agreement between WHO and the Department of Health and Human Services. Three WHO Collaborating Centers, established under the Bureau of Radiological Health, continue to function under NCDRH: WHO Collaborating Center for Standardization of Protection Against Nonionizing Radiations; WHO Collaborating Center for Training and General Tasks in Radiation Medicine; and WHO Collaborating Center for Nuclear Medicine. We welcome your comments and requests for further information. (jn C. Villforth Director National Center for Devices and Radiological Health ii ''PREFACE The selection of patients for x-ray examinations is a key factor in the radiological process, initiating events which will produce radiation exposure of the patients and generate radiological information. The questions involved, such as whether an x-ray examination is needed, what type, and how the information generated will help in patient management, often have no straightforward answers. The Food and Drug Administration's National Center for Devices and Radiological Health supports several efforts to investigate the effectiveness of certain x-ray examinations in providing clinical information needed to aid physicians in clinical decision making. One particularly significant effort is the convening of panels of physicians to examine certain specific x-ray examinations as to their efficacy and to suggest, if possible, referral criteria to optimize their use. This publication is the second in a series of publications presenting Panel- developed recommendations on selected x-ray examinations. The first, entitled The Selection of Patients for X-ray Examinations: The Pelvimetry Examination (HHS Publication (FDA) 80-8128). (GPO: 017-015-00174-1; NTIS: PB 81-113490, microfiche only) was published in July 1980. It is intended that subsequent referral criteria statements be developed in a manner similar to the development of the chest x-ray screening statements presented here and the previously published pelvimetry statement. This process involves a close, cooperative interchange between the Public Health Service, the American College of Radiology, and other relevant professional societies, utilizing available scientific literature and searching for possible clinical consensus. The referral criteria statements and the rationale for their development are made available to concerned persons for the purpose of stimulating additional research and providing valuable information for clinicians. We hope that the statements and the accompanying background material will be of value for medical students, practicing physicians, and other persons interested in the efficacious use of medical radiation. We also encourage interested parties to read the related general document The Selection of Patients for X-ray Examinations (HEW Publication (FDA) 80-8104). (NTIS: PB 80-157431, $10.00 paper copy, $4.50 microfiche). ert William S. Propeérzio//Ph.D. Acting Director Office of Training and Assistance iv ''CONTENTS Foreword .......... eeb eee ees aoe ce coe ee ee ecectaees eae seceese es Seeses iii Preface... .ccccccccccesecceces capsedsonne ope Pee a eee Ae acae » + keene one iv Abstract ......cccccccccveee oe eee eee cence Ceeesee Poorer ecc ce ccceceece vi Acknowledgments ........cccccecccceees tb pew ee bie pO eee cece cee cee ee eee vii Introduction ........ceeeeeeee pec c een acceecescccsone see ccc eeteecsesces 1 The Concept of Referral Criteria... .... ccc c cece cece eee ccccecccececees 2 Background and Issues Stimulating the Formation of the Chest X-ray Panel......... eeeeceeecees ep 340.0 Xbb beeen eedoneuse ba 3 The Report of the Chest X-ray Panel .........cccccceccccccccccccvcececes 9 Overview ......... Sete ssececeses ce esees ceaewce oes cece sscnnicccece 11 Statement 1. Mandated Routine Screening Chest X-Ray Examinations ........ccccecececees eevee eecesseesecs 13 Statement 2. Routine Prenatal Chest X-Ray Examinations........... 19 Statement 3. Routine Hospital Admission Chest X-Ray EXaMinations ....... ccc cece ccc ceccccececcccccsececs 23 Statement 4. Chest X-Ray Examinations for Tuberculosis Detection and Control .....ccccccccccccccccccccecvcs 27 Statement 5. Chest X-Ray Examinations in Occupational MeICING ..... cece cc we ccc cece ccc eees co cewesnece 31 Appendices A. Consultants to the Chest X-Ray Panel .........ccccccccccccccccces 34 B. Announcements of the Draft Chest X-Ray Referral Criteria Panel Report and Categories of Requests for the Chest X-Ray Referral Criteria Panel Report .............00. 35 C. Professional Medical Organizations Involved in Reviewing the Draft Chest X-Ray Referral Criteria Panel Report...... cc cece cece cece ccc ec ccc ec cecccccceces 36 D. American Thoracic Society Recommendations: "Control of Tuberculosis". ....... cece cece cece etc e ccc eccececceees 37 E. American Thoracic Society Recommendations: "Treatment of Tuberculosis And Other Mycobacterial Diseases" ......... cece ccc e cece cece ec ec cscsecees 45 ''ABSTRACT Department of Health and Human Services, National Center for Devices and Radiological Health. The Selection of Patients for X-ray Examinations: Chest X-Ray Screening Examinations. HHS Publication FDA 83-8204 (August 1983) (pp. 51). Five chest x-ray referral criteria statements have been developed and unanimously endorsed by a panel of physicians convened as part of a major voluntary cooperative effort between FDA's National Center for Devices and Radiological Health (NCDRH) and the medical professional community. The referral criteria statements include recommendations concerning the following applications of chest x-ray screening: mandated routine chest x-ray screening examinations, routine prenatal chest x-ray examinations, routine hospital admission chest x-ray examinations, chest x-ray examinations for tuberculosis detection and control, and routine chest x-ray examinations for occupational medicine. The complete text of the five referral criterial statements plus a brief discussion of the rationale for the development of each statement is presented. vi ''ACKNOWLEDGMENTS The following individuals contributed substantially to the development of the Chest X-ray Referral Criteria Statements: Chest X-Ray Panel Reynold F. Brown, M.D. - Chairman Norman J. Ashenburg, M.D. John A. Campbell, M.D. John M. Eisenberg, M.D. Laurence S. Farer, M.D., M.P.H. David Glasser, M.D., M.P.H. Reginald Greene, M.D. Donald G. Nikolaus, M.D. Gerald Parker, P.E. Holger Rasmussen, M.D. Carl E. Ravin, M.D. Lee B. Reichman, M.D., M.P.H. E. Nicholas Sargent, M.D. American College of Radiology Robert D. Moseley, Jr., M.D. Radiological Health Sciences Education Project John W. Shaver, M.S. National Center for Devices and Radiological Health Joseph S. Arcarese, M.S. James L. Morrison, M.S. Jay A. Rachlin, M.S. Harvey Rudolph, Ph.D. vii '' ''THE SELECTION OF PATIENTS FOR X-RAY EXAMINATIONS CHEST X-RAY SCREENING EXAMINATIONS INTRODUCTION In 1978, a National Conference on Referral Criteria for X-Ray Examinations was cosponsored by Congressman Paul Rogers, Chairman of the Subcommittee on Health and the Environment, and the Secretary of Health, Education, and Welfare (6). The conference brought together representatives of health-related government agencies, State health departments, medical professional organizations, third party carriers, and the legal profession. A forum was provided for the exchange of ideas and discussion of causes of x-ray overuse and the role of x-ray referral criteria in limiting x-ray exposure and containing health care costs. Workshop sessions were held to address specifie issues in detail and to formulate plans whereby government and the private sector could work cooperatively to provide solutions. One of the principal recommendations of the Conference was that small physician panels, composed of representatives from appropriate medical specialty societies should be convened to develop referral criteria for specific diagnostic x-ray examinations. The role of government was identified as the facilitator, i.e., the collector of data and provider of resources for the physician panels. Following this Conference, the Bureau of Radiological Health (now the National Center for Devices and Radiological Health (NCDRH)), of the Food and Drug Administration, asked the Radiological Health Sciences Education Project (RHSEP), University of California, San Francisco, to establish an expert panel to develop referral criteria for the chest x-ray examination.* The NCDRH and RHSEP mutually agreed to focus on the area of administratively required examinations, i.e., chest x-ray examinations required either by regulation or by administrative protocol. A Chest X-ray Panel was convened, consisting of representatives from family practice, internal medicine, pulmonary medicine, occupational medicine, radiology, tuberculosis control, and public health. (A list of Chest X-ray Panel members and their professional affiliation is given in the section entitled Report of the Chest X-ray Referral Criteria Panel). The first meeting of the Chest X-ray Panel was held in April 1979. At this initial meeting, the panelists identified eight subcategories of asymptomatic chest x-ray screening for review. After considerable discussion, study, and debate during subsequent panel meetings, five statements concerning the use of chest x-ray screening examinations were developed and endorsed by the Panel. The National Center for Devices and Radiological Health acted as the facilitator for the development of the referral criteria by providing the financial resources to *Under the terms of FDA Contract No. 223-81-6001 ''hold the panel meetings and by providing staff work as requested by the Chest X-ray Panel. The NCDRH staff prepared a comprehensive overview report of the chest x-ray screening issues and a thorough literature review of pertinent references. The RHSEP acted as the secretariat by arranging the meetings, preparing minutes, and providing other technical, clerical and editorial support to the Panel. The complete report of the Chest X-ray Panel including their specific recommendations is contained in this document. The Chest X-ray Panel met seven times between 1979 and 1981. During its deliberations, the Panel also requested the advice of outside experts. Representatives of organized labor, government agencies, such as the Occupational Safety and Health Administration, and the Health Care Financing Administration, as well as other medical professionals not represented on the Chest X-ray Panel, were invited to attend meetings and made significant contributions. (Appendix A lists the Chest X-ray Panel Consultants.) In June 1981, the NCDRH announced in the Federal Register the availability for review of the Draft Chest X-ray Panel Report (3). In addition, the availability of the report was announced in other bulletins and newsletters (Appendix B). In all, over 600 copies of the report were requested and distributed by NCDRH. (Appendix B also lists the categories of requests for the report.) The letters and comments received were carefully reviewed and analyzed by the Chest X-ray Panel resulting in several changes in the recommendations. Coneurrent with this public sector review, the American College of Radiology (ACR) coordinated a review among medical specialty societies. The 1978 National Conference had recommended that radiologists coordinate such efforts and the ACR accepted this role and assigned the responsibility to their Radiation Advisory Committee under the chairmanship of Robert D. Moseley, Jr., M.D. Dr. Moseley's committee contacted and distributed copies of the report to 19 medical specialty organizations for review (Appendix C). The comments received from these organizations were transmitted to the Chest X-ray Panel members for their consideration, and these comments resulted in several clarifying changes. Following an analysis of all comments, the Chest X-ray Panel prepared the final report that is contained in this publication. This report was in turn distributed by Dr. Moseley to the medical specialty organizations for their consideration of adoption or endorsement. The general comments received by Dr. Moseley indicated that the report was "eminently sensible." Since then, several organizations have adopted the full report, such as the American Academy of Family Physicians and the American College of Radiology; and other organizations have adopted that portion of the report pertaining to their specialty, e.g., the American College of Obstetricians and Gynecologists has adopted the prenatal chest x-ray statement. In accordance with the National Conference recommendation, the Food and Drug Administration, U.S. Public Health Service, is publishing this report of the Chest X-ray Referral Criteria Panel. THE CONCEPT OF X-RAY REFERRAL CRITERIA X-ray examinations can define the type and extent of disease in many clinical situations. Chest x-ray examinations generally do not result in patient discomfort, are not invasive, and are relatively easy to perform. However, public and professional concern over the potential risks from radiation exposure and the increasing costs of x-ray examinations have led to studies of methods to reduce unproductive examinations, i.e., examinations that do not yield information useful to patient care decision making. Unproductive x-ray examinations should not be equated with negative examinations. Negative examinations can be very useful and can contribute significantly to patient care. Significant reductions in patient radiation exposure from ''x-ray examinations have occurred and will continue to occur with advances in technology. Nevertheless, x-ray examinations of necessity involve some x-ray exposure to the patient, and while chest x rays individually are low dose examinations, collectively, they contribute significant population dose. Therefore, before an x-ray examination is requested, physicians should judge whether it has an acceptable probability of affecting patient care. Professional, patient, and medicolegal pressures complicate the situation and sometimes influence physicians to refer patients for x-ray examinations they might otherwise consider unnecessary. One approach to reducing unproductive x-ray examinations which has been recommended by a number of clinicians is the development and use by referring physicians of carefully developed statements on use, or referral criteria, for those particular examination circumstances where the diagnostic benefits are unclear or questionable. Such guidelines can be helpful to physicians in deciding when to obtain x-ray examinations. These guidelines should be developed by consolidating the experience of many practitioners and they should be validated by testing in a variety of clinical settings. The use of appropriate referral criteria can minimize those instances in which the results of the diagnostic x-ray examination prove to be unproductive. The availability of published referral criteria can also assist physicians in resisting any real or perceived external pressures to order diagnostic x-ray examinations against their clinical judgment. Referral criteria are not intended to be requirements or regulations but only to offer guidance based upon careful analysis of the scientific literature. BACKGROUND AND ISSUES STIMULATING THE FORMATION OF THE CHEST X-RAY PANEL The chest x-ray examination is the most frequently performed x-ray examination in the United States. It is a component of most periodic physical examinations, and has, in many cases, become an automatic requirement in the health evaluations conducted by Federal, State, and local governments, and private sector groups. The NCDRH's X-ray Exposure Study showed that in 1970, chest x-ray examinations accounted for approximately 45 percent of all medical x-ray examinations (5). More recently, NCDRH's Radiation Experience Data (RED) program estimated that in 1980, 52 million chest x-ray examinations were performed in United States hospitals (8). In one frequently cited study analyzing more than 10,000 chest x-ray examinations investigators determined that over 6000, or about 60 percent, of the chest x-ray examinations conducted were performed for routine screening purposes (13). If this percentage were applied to the RED data, we would estimate that over 30 million routine screening chest x-ray examinations were performed in U.S. hospitals during 1980. A significant number of chest x-ray examinations are also performed in other settings, such as private physicians' offices and clinics. A large number of these chest x-ray examinations may also be screening examinations, for example, annual health examinations. In another study conducted at Michigan State University, chest x-ray examinations administratively required for employment purposes comprised approximately 28 percent of all chest x-ray examinations in the State of Michigan (12). Using an average cost of $25 per examination, the cost of these employment- related chest radiographs was estimated to be more than $8 million. As health costs continue to rise, money and medical resources must be used efficiently. Therefore, it is increasingly important that the use of diagnostic x-ray screening examinations in asymptomatic populations be reviewed to determine if the utility justifies the cost. The ability of the chest x-ray examination to determine the status of the chest is rarely questioned. Its reliability in demonstrating chest disease in symptomatic patients has led to the belief that the examination can be used to detect chest disease ''in asymptomatic persons without any additional clinical information. Even though this may be true, the maximum productivity of any screening test is the prevalence of existing disease in the asymptomatic population. The usefulness of the chest x-ray examination in screening may be limited by this fact. The use of chest x-ray examinations to detect abnormalities in unselected population groups is based on two assumptions: 1. there are diseases or abnormal conditions that can be detected in a "silent" (i.e., asymptomatic) phase, and 2. the disease or abnormality detected can be treated and such treatment significantly reduces future morbidity and mortality. TUBERCULOSIS DETECTION Between 1945 and 1955, chest x-ray examinations of asymptomatic populations, performed primarily for tuberculosis detection, increased markedly. Many of these examinations were conducted using photofluorographic or minifilm systems (the use of minifilms is generally credited with improving tuberculosis case-finding during this period). The success of this endeavor resulted in the mandating of periodic chest x-ray examinations in many occupations where contact with the public was significant, e.g., food handlers, teachers, ete. A recent survey of State health officers identified more than 20 broad occupational groups that are required by law or regulation to have periodic chest x rays (11). And a survey of 624 student health services showed that preenrollment and periodic radiographic screening remains prevalent in United States colleges and universities. Over half (52 percent) of the schools surveyed screen all co students and over one quarter (27 percent) screen all students periodically 9). Over the past twenty to thirty years, however, the treatment for tuberculosis has vastly improved and tuberculin skin testing has become a reliable indicator of tuberculous infection. These developments have resulted in a decrease in the. prevalence of undetected tuberculosis in the general population and a reevaluation of the use of chest x rays for tuberculosis case finding and control. In 1972, the Department of Health, Education, and Welfare in conjunction with the American College of Radiology and the American College of Chest Physicians recommended that "mass screening of the general population for tuberculosis and other chest diseases should not be done in view of the undesirability of using radiation without clear evidence of a significant benefit. In recent years, the value of such screening programs has become suspect because of the relatively few cases of cardiopulmonary disease, particularly active tuberculosis discovered through their use" (4). The Surgeon General of the U.S. Public Health Service attempted to further reduce unproductive chest x-ray examinations in the Federal sector. In 1980, he wrote to the various Federal agencies announcing that he was discontinuing routine chest x-ray examinations performed for Public Health Service (PHS) employees and requesting that other Federal agencies review their requirements for routine chest x- ray screening. This request resulted in the elimination of 32,000 routine asymptomatic chest x-ray examinations per year in the PHS and 128,000 outside the PHS, at a cost savings conservatively estimated at $4 million annually (2). In addition, a recent study conducted by the Baltimore City Health Department disclosed that, between 1975 and 1979, the incidence of tuberculosis (TB) among the ''employed population in Maryland was significantly lower than that of the Maryland general population (10). Moreover, no sizeable occupational group, targeted by laws and regulations in one or more of 32 States responding to a national survey, experienced significantly higher tuberculosis incidence rates than the unscreened general population. This study disclosed several significant facts. For example, two frequently targeted occupations, nursing home and school employees, were found, respectively, to be at 1/6th and 1/3rd the risk of developing TB relative to the general population. When investigated in greater detail, no nursing home employees and only 18 percent* of school employees with communicable TB were discovered as a result of the screening mandate. For school employees, the cost of detecting one case of communicable TB during this 5-year period ranged between $2,123,000 and $3,756,000. Data from this Baltimore City Health Department study were sufficiently compelling that the traditional practice could no longer be justified epidemiologically, economically, or in terms of radiation exposure. Maryland public health officials acted affirmatively to abrogate the requirement that hospital employees be certified as "free from tuberculosis in a communicable state," and major State legislation was enacted in July 1983 in an attempt to eliminate the mandatory requirement that nursing home and school employees be certified as being free of TB infection. There are, however, selected populations where tuberculosis screening may still be indicated. For example, the tuberculosis prevalence among emigrants from certain foreign countries remains at a level sufficient to justify the continued screening of these groups. In 1982, the American Thoracic Society (ATS) published a series of recommendations regarding screening for adult respiratory disease. These have been reprinted in Appendix D. In addition, the American Thoracie Society's official statement for the treatment of tuberculosis and other mycobacterial diseases has been reprinted in Appendix E. This statement presents information on the current methods and techniques for designing and operating tuberculosis screening programs in those populations where screening has been determined to be effective. LUNG CANCER DETECTION Chest x-ray screening examinations have been widely used for the early detection of lung cancer. Recently, however, this practice has been called into question. The American Cancer Society in 1980 changed its former policy and concluded "not to recommend the use of annual chest x-rays to sereen asymptomatic people for lung cancer" (1). The basis for this reeommendation derives from the National Cancer Institute's Consensus Conference on Mass Screening for Lung Cancer (7). Interim results of controlled clinical trials indicated that overall lung cancer mortality has been unaffected by chest x-ray screening programs. The reader should note, however, that studies are still ongoing to determine whether the survival rates in lung cancer victims may be affected by appropriately designed screening programs. Today the critical evaluation of the efficacy of various medical examinations has become a necessary activity. Although the chest examination is only one of several radiological tests undergoing review, it is of particular importance because of the large number of chest x-ray examinations conducted annually. This document presents the chest x-ray screening referral criteria statements as developed by a panel of physicians expert in the examination's use. We hope that this *Two communicable cases of tuberculosis were detected through screening out of 11 newly developed cases of communicable tuberculosis (18 percent). A total of 46 newly developed cases of tuberculosis (ecommunicable/noncommunicable) were found out of 653,203 sereened school employees. ''information will prove beneficial to health care decision makers who deliberate the usefulness of chest x-ray screening. ''3. 6. 10. 11. 12. 13. REFERENCES American Cancer Society. ACS report on the cancer-related checkup: cancer of the lung. CA-A Cancer Journal for Clinicians 30:199-207 (July/August 1980). BRH-Directed Efforts Eliminate 160,000 Unnecessary Chest X Rays Annually. BRH Bulletin XV:4:1 (March 9, 1981). Chest X-ray Referral Criteria Panel Draft Report; Availability. Notice of Availability. Federal Register 46 FR 30568-30570 (1981). Department of Health, Education, and Welfare, Bureau of Radiological Health. The Chest X ray as a Screening Procedure for Cardiopulmonary Disease: A Policy Statement. HEW Publication (FDA) 73-8036 (April 1973). Department of Health, Education, and Welfare, Bureau of Radiological Health. Population Exposure to X rays, U.S. 1970. HEW Publication (FDA) 73-8047 (November 1973). Department of Health, Education, and Welfare, Bureau of Radiological Health. National Conference on Referral Criteria for X-ray Examinations. HEW Publication (FDA) 79-8083 (April 1979). Department of Health, Education, and Welfare, National Institutes of Health. Consensus Development Conference Summaries. Volume 1, 1977-1978. Department of Health and Human Services, National Center for Devices and Radiological Health. Radiation Experience Data (RED) Program. Unpublished data (1980). Fager, S.S., G.B. Slap, D.S. Kitz, and J.M. Eisenberg. Sereening for Chest Disease in College Students: Policies of Student Health Services Regarding the Use of Routine Screening Chest Radiographs and Tuberculin Skin Tests. Am J Pub Health (in press). Glasser, D. Mandated chest x-ray screening of employees for tuberculosis detection. Am Rev Respir Dis 125:(Suppl.) 184 (1982). McBurney, R.E., M.A. Wollerton, J.A. Rachlin, and J.R. Fisher. Prevalence of Administrative X Rays: Results of a Nationwide Survey. Presented at the Conference of Radiation Control Program Directors, Inc. Annual Meeting. Reno, NV (May 1983). Potechen, E.J., J.W. Gard, et al. The Utility of Administrative Diagnostic X rays. HHS Publication (F DA) 82-8194 (August 1982). Sagel, S.S., R.G. Evens, J.V. Forrest, and R.T. Bramson. Efficacy of routine sereening and lateral chest radiographs in a hospital-based population. N Engl J Med 291:1001-1004 (November 7, 1974). '' TY ''REPORT OF THE CHEST X-RAY REFERRAL CRITERIA PANEL This report has been prepared at the request of the National Center for Devices and Radiological Health (NCDRH). The following individuals contributed substantially to its development. Chest X-Ray Panel Reynold F. Brown, M.D., Chairman Department of Radiology University of California San Francisco Norman J. Ashenburg, M.D. Corporate Medical Director Eastman Kodak Company John A. Campbell, M.D. Chief, Department of Radiology Martin Luther King, Jr. Hospital John M. Eisenberg, M.D. Chief, Section of General Medicine University of Pennsylvania Laurence S. Farer, M.D., M.P.H. Director, Division of Tuberculosis Control Center for Prevention Services Centers for Disease Control David Glasser, M.D., M.P.H. Director, Bureau of Disease Control City of Baltimore Health Department Reginald Greene, M.D. Department of Radiology Massachusetts General Hospital Donald G. Nikolaus, M.D. Family Practice Mease Hospital & Clinic Gerald Parker, P.E. Director, Radiation Control Program Massachusetts Department of Public Health Holger Rasmussen, M.D. Family Practice Fremont, California Carl E. Ravin, M.D. Department of Radiology Duke University Medical Center Lee B. Reichman, M.D., M.P.H. Director of Pulmonary Division University of Medicine and Dentistry of New Jersey E. Nicholas Sargent, M.D. Department of Radiology University of Southern California ''American College of Radiology Robert D. Moseley, Jr., M.D. Department of Radiology University of New Mexico Radiological Health Sciences Education Project John W. Shaver, M.S. National Center for Devices and Radiological Health Joseph S. Arcarese, M.S. James L. Morrison, M.S. Jay A. Rachlin, M.S. Harvey Rudolph, Ph.D. The members of the Panel express their appreciation to Joseph Arcarese, James Morrison, Harvey Rudolph, and Jay Rachlin of the Office of Training and Assistance, NCDRH, and other members of their staff and the staff of the RHSEP who so ably assisted the Panel by providing technical support and administrative assistance whenever required. They also analyzed and carefully collated the many comments received during the review to ensure that each issue was thoroughly considered. 10 ''OVERVIEW The development and use of referral criteria for x-ray examinations is highly desirable for ensuring appropriate use of medical resources, optimizing patient care, and minimizing the medical radiation burden. Development of referral criteria for chest x-ray examinations is most important because these examinations are the most frequently performed x-ray study (accounting for approximately 45 percent of all examinations). Chest x-ray examinations are also the most likely to be performed on asymptomatic subjects, and the most common studies mandated by government, industry, and hospital policy. This report exclusively addresses administratively mandated routine chest x-ray screening examinations. The principal task of the Chest X-ray Panel was to assess critically the efficacy of mandated chest x-ray screening programs, many of which are performed in the absence of other medical evaluation (e.g., patient history, physical examination, or other diagnostic tests). While such screening programs have been conducted for many years, an extensive review of the current literature indicates a disappointingly low yield of both previously undiagnosed disease and patient benefit. In some chest x-ray screening programs (e.g., those for tuberculosis), the disease prevalence in the general population has declined to such an extent that the programs are not efficacious. Therefore, it is difficult to justify continuation of such programs. The vast majority of significant medical illnesses are discovered through the evaluation of suggestive symptoms. It is hoped, therefore, that the use of referral criteria based on environmental exposure, other appropriate history, physical findings, or relevant diagnostic tests will substantially improve the yield from chest x-ray examinations. Limiting examinations to appropriately selected populations promises to reduce the large medical and financial burden of studying unselected low-yield populations where the impact of false-positive diagnoses may offset any possible overall gain. However, the following conditions must be borne in mind with regard to the use of these particular referral criteria: 1. the referral criteria developed by the Chest X-ray Panel apply only to groups that are being evaluated for the detection or control of specific diseases or to provide a baseline because of future assumed risk; 2. they do not apply to selected groups that have been established as high risk populations (e.g., miners, asbestos workers, immigrants to the U.S. from selected areas); 3. they do not apply to an individual patient seen by a physician for specific signs and/or symptoms; and 4. they do not apply to an individual seen by a physician for a periodic health appraisal. 11 ''35 Glossary Of Terms As used in this report, the following definitions apply: Sereening Programs: Testing of unselected populations (i.e., of individual participants not selected according to risk of disease). Specific Diagnostic Testing: Examinations such as skin testing, urinalysis, electrocardiogram, sputum examination, etc. Selected Populations: Groups identified by epidemiologic characteristics, history, physical examination, or specific diagnostic testing in whom a significant diagnostic yield is established or is likely. (Note that significant yield cannot be characterized by a single numerical value but rather is a funetion of the cost and risk of the examination weighed against potential medical benefit.) Each of the following five referral criteria statements is preceded by a brief discussion of the rationale for its development. The reader may note some redundancy but this is necessary so that each statement may stand alone. 12 ''MANDATED ROUTINE SCREENING CHEST X-RAY EXAMINATIONS RATIONALE Policies mandating chest x-ray examinations for screening or administrative purposes have added significantly to radiographic usage over the past several decades. The reliability of x-ray studies in demonstrating disease in symptomatic patients led to the belief that they could be used to detect disease in asymptomatic persons without the benefit of additional clinical information or without regard to the prevalence of existing disease in given populations. Such mandated x-ray examinations have spread through every segment of society: hospitals, industry and places of employment, the military, schools, governmental agencies, and charitable organizations. Many individuals and organizations other than physicians have become involved in the process of determining who should be radiographed. For example, government mandates radiographic studies in certain occupations; industry frequently requires preemployment or preplacement films; hospitals may require admission chest x-ray examinations of all patients, ete. Reports in the medical literature of experience with mandated chest x-ray screening examinations have shown that the yield of unsuspected disease is extremely low, except in occasional groups where a higher prevalence of disease is known to exist, e.g., elderly disadvantaged citizens, immigrants from underdeveloped countries, heavy cigarette smokers, etc. In recognition of this fact, the American Cancer Society recently discontinued its recommendation for an annual chest x-ray examination on asymptomatic persons because no improvement in lung cancer mortality had resulted from this practice. Furthermore, the high frequency of the examination, cost-benefit considerations, radiation exposure, and_ subject inconvenience are pressures for the more selective use of mandated chest x-ray screening programs. The motivation for the discovery of unsuspected disease in apparently healthy persons is based on the assumptions that early detection increases the cure rate, avoids the cost of prolonged medical care, reduces epidemic spread, and generally improves the quality of health in society. Scientific data, however, shows these premises to be false in many instances. For example, a comprehensive audit of the Kaiser Permanente multiphasie screening program showed that the only tests with a worthwhile yield of silent diseases were urine analysis, blood pressure determination, and stool testing for occult blood. Many mandated chest x-ray screening programs have been established either to assure employers that unsuspected disease does not exist prior to or during employment, or, similarily, to assure health care providers and their recipients that unsuspected disease does not exist prior to the delivery of medical services. Such programs have usually been initiated without documentation that these x-ray examinations would, in fact, disclose a significant yield of occult disease. Likewise, it has not been determined in controlled studies whether such case finding would improve patient outcome, alter therapeutic management, or affect employer liability. Asa result, chest screening x-ray examinations have become an accepted part of protocols for employment, hospital admission, etc., without establishing their true value. Other factors that offset the potential usefulness of chest x-ray screening programs are the decreasing prevalence and highly effective therapy of pulmonary tuberculosis, the recognition of less costly alternatives to radiography (e.g., skin testing or sputum culture), and the vastly improved public health personnel safety regulations in industry, schools, and government. Today, it seems wiser to base such routine screening examinations only on substantiated yields in selected populations or where selection by specific diagnostic testing or history enhances the yield. 13 ''The Chest X-ray Panel has defined the following conditions and situations for which "mandated chest x-ray examinations of asymptomatic populations" would be useful: 1, 2. The disease has a silent phase, i.e., the disease is present although no signs or symptoms exist. The disease can be diagnosed, in the silent phase, by x-ray examination at a frequency that is cost-effective for the population being examined. For example, it is known that lung cancer has a silent phase (condition 1 above). Chest x-ray examinations may find silent disease at a cost-effective rate in heavy smokers selected by age, but not in general populations selected by age only. The disease can be effectively treated at the time of diagnosis. Mesothelioma, for example, is a disease where early diagnosis may not be useful since it cannot be effectively treated when diagnosed. The thoracic, cardiovascular, and pulmonary status is considered useful information, not for current disease detection, but as a reference baseline in evaluating future changes and determining the time period for changes to occur. There is an expectation of finding abnormal anatomical conditions susceptible to management or correction. This usually refers to congenital or acquired silent conditions. 14 ''REFERRAL CRITERIA STATEMENT FOR MANDATED ROUTINE SCREENING CHEST X-RAY EXAMINATIONS There are a variety of instances where free-standing screening chest x-ray examinations are performed on asymptomatic persons solely because of administrative mandate or protocol. This practice is based on the assumption that significant disease can be detected in a silent phase when it is more amenable to successful medical treatment. The productivity of mandated chest x-ray examinations in random asymptomatic populations is dependent on the prevalence of disease in those populations and whether its detection does, in fact, significantly reduce morbidity and mortality. The yield of unsuspected disease (e.g., lung cancer, heart disease, and tuberculosis) found by routine mandated chest x-ray screening examinations of unselected populations, not based on history, physical examination, or specific diagnostic testing, has been shown to be of insufficient clinical value to justify the monetary cost, added radiation exposure, and subject inconvenience of the examination. IT IS THEREFORE RECOMMENDED THAT ALL SUCH MANDATED ROUTINE SCREENING EXAMINATIONS OF UNSELECTED POPULATIONS BE DISCONTINUED, UNLESS A SIGNIFICANT YIELD CAN BE SHOWN. This statement does not preclude chest x-ray examinations based on individual history, physical examination, or specific diagnostic testing (e.g., sputum cytology, electroeardiography, and skin test), or in selected populations shown to have significant yields of previously undiagnosed disease. 15 ''10. 11, 12. 13. 14. 15. 16. References Affeldt, J.E. JCAH Hospital Admissions Policies (Q & A). Hospitals 53:44. (June 16, 1979). American Cancer Society. ACS report on the cancer-related health checkup: Cancer of the lung. CA-A Cancer J Clinicians 30:199-207. (July/August 1980). American Occupational Medical Association, Energy Technology Committee. Guidelines for use of routine x-ray examinations in occupational medicine: Committee Report. JOM 21: 500-502 (July 1979). Baker, D.H., W.E. Berdon, and S.M. Sane. Routine chest x-ray examination? (Letters). Pediatrics 62:659-660 (November 1978). Boucot, K.R. and W. Weiss. Is curable lung cancer detected by semiannual screening? JAMA 224:1361-1365 (June 4, 1973). Department of Health, Education, and Welfare, Bureau of Radiological Health. The Chest X ray as a Screening Procedure for Cardiopulmonary Disease: A Policy Statement. HEW Publication (FDA) 73-8036 (April 1973). Feingold, A.O. Routine chest roentgenograms on hospital admission do not discover tuberculosis. South Med J 70:579-580 (May 1977). Florin, A.A., J. P. Harkness, J. G. Collins, and M.H. Burton. Heart sereening in the Newark Model Cities area: A feasibility study. Am J Public Health 61:1130- 1139 (June 1971). Greene, R.; Larsen, P.D.; Shapiro, S.H. and H.P. Pendergrass; and Sagel, S.S. Screening with chest radiographs (Series of Letters). N Engl J Med 292:435-437 (February 20, 1975). LaDou J., J.N. Sherwood, and L. Hughes. Multiphasie health testing: Benefit- cost analysis of high-volume and low-volume testing programs. JOM 17:495-501 (August 1975). Lung cancer screens nixed by NCI (News brief). Med World News 19:32 (October 16, 1978). Mackenzie, C.J.G. A two-year follow-up of persons with non-tuberculous chest disease found at "Operation Doorstep," Vancouver, 1964. Can Med Assoc J 103:1019-1025 (November 7, 1970). Martin, P.D. Regular chest x-rays (Letter). NZ Med J 86:493 (November 23, 1977). Miller, A.B. Screening for lung cancer. Can J Public Health 64(2 Suppl):532-535 (March 1973). National Tuberculosis and Respiratory Disease Association. Chest x-ray screening recommendations for TB-RD Associations: A statement by the NTRDA Committee for the guidance of the tuberculosis program (Policy statement). NTRDA Bulletin 57:3 (October 1971). Neumann, H.H. Tuberculosis control policies in transition. HSMHA Health Reports 86:1007-1010 (November 1971). 16 ''17. 18. 19. 20. 21. 22. 23. 24. 25. Petterson, S.R. and M.L. Janower. Is the routine pre-operative chest film of value? Applied Radiology 6:70 (January-February 1977). Polk, L.D. No more mass x-ray screening for tuberculosis. Clin Pediatr 15:983- 985 (November 1976). Preoperative chest radiology: National study by the Royal College of Radiologists. Lancet 2:83-86 (July 14, 1979). Routine chest radiogaphs (Editorial). Lancet 1:83-84 (January 11, 1975). Sagan, L.A. Routine chest x-ray film (Letter). JAMA 220:278 (April 10, 1972). Sagel, S.S., R.G. Evens, J.V. Forrest, and R.T. Bramson. Efficacy of routine screening and lateral chest radiographs in a hospital-based population. N Engl J Med 291:1001-1004 (November 7, 1974). Schneider, W.J. and M. Dykan. : The preplacement medical evaluation of hospital personnel. JOM 20:741-744 (November 1978). Toman, K. Mass radiography in tuberculosis control. WHO Chron 30:51-57 (February 1976). Weiss, W., H. Seidman, and K.K. Boucot. The Philadelphia Pulmonary Neoplasm Research Project. Am Rev Respir Dis 111:289-297 (March 1975). 17 '' ''ROUTINE PRENATAL CHEST X-RAY EXAMINATIONS RATIONALE The more effective use of mandated x-ray screening chest films is being examined closely by various public health agencies from the standpoint of high volume and cost-benefit considerations, radiation exposure, and subject inconvenience. Motivations for the discovery of unsuspected disease in well persons based on the assumption that early detection increases the cure rate, avoids cost of prolonged medical care, reduces epidemic spread, and generally improves the quality of health in society, is not supported by scientific data in most instances. In a nonpregnant, mixed population (younger than 20 years of age), routine radiography has been shown to be unproductive in the absence of any clinical reason to suspect chest disease (8). Traditional reasons for prenatal sereening to identify patients with pulmonary tuberculosis are no longer valid (1,2,5,7). Tuberculosis rates both in the general population and in this selected population have greatly declined (3,5). Studies of large numbers of pregnant subjects reveal an extremely low incidence of cardiac or pulmonary abnormalities and an even lower incidence of pulmonary tuberculosis (1,2,5,7). In almost every case, a positive history, abnormal physical findings, or specifie diagnostic testing (e.g. skin test) would have suggested the presence of major abnormality and/or the need for radiography. Cumulative exposures to low levels of diagnostic radiation are theorized to increase risk of leukemia and other diseases in the exposed individuals (4,6,9). In the ease of prenatal chest x-ray examinations, it would be possible for both the mother and fetus to be exposed. However, it should be noted that the dose from a properly conducted chest x-ray examination is small and if proper collimation is used, the fetus is generally not exposed. Although the radiation exposure to the fetus may not be a consideration, the mother's stress and anxiety may be a factor. Because tuberculin skin testing offers virtually no risk and is effective, it should be substituted for radiographic screening of pregnant patients for pulmonary tuberculosis. 19 ''REFERRAL CRITERIA STATEMENT FOR ROUTINE PRENATAL CHEST X-RAY EXAMINATIONS The yield of unsuspected disease found by routine chest x-ray examination of unselected pregnant patients (i.e., by protocol or by mandate) has been shown to be of insufficient clinical value to justify the radiation exposure, inconvenience to the pregnant patient, and monetary cost. IT IS THEREFORE RECOMMENDED THAT ALL SUCH ROUTINE PRENATAL CHEST X-RAY EXAMINATIONS BE DISCONTINUED. This statement does not preclude prenatal chest x-ray examinations based on individual history, physical examination, or specific diagnostic testing, or in selected populations shown to have significant yields of previously undiagnosed disease. 20 '' 1. 3. References Bonebrake, C.R., K.L. Noller, C.P. Loehnen, J.R. Muhm, and C.R. Fish. Routine chest roentgenography in pregancy. JAMA 240:2747-2748 (December 15, 1978). Campbell, J.A. Retrospective study of 2000 prenatal chest x rays. Personal communication. (unpublished data). Department of Health, Education, and Welfare, Bureau of Radiological Health. The Chest Xray as a Screening Procedure for Cardiopulmonary Disease: A Policy Statement. HEW Publication (FDA) 73-8036 (April 1973). Graham, S., M.L. Levin, A.M. Lilienfeld, L.M. Schuman, R. Gibson, J.E. Dowd, and L. Hempelmann. Preconception, intrauterine, and postnatal irradiation as related to leukemia. Natl Cancer Inst Monogr 19:347-371 (1966). Hadlock, F.P., S.K. Park, and R.J. Wallace. Routine radiographic screening of the chest in pregnant women: Is it indicated? Obstet Gyn 54:433 (1979). MacMahon, B. Prenatal x-ray exposure and childhood cancer. J Natl Cancer Inst 28:1173-1191 (May 1962). Mattox, J.H. The value of a routine prenatal chest x-ray. Obstet Gyn 41:243- 245 (February 1973). Sagel, S.S., R.G. Evens, J.V. Forrest, and R.T. Bramson. Efficacy of routine screening and lateral chest radiographs in a hospital-based population. N Engl J Med 291:1001-1004 (November 7, 1974). Stewart, A., J. Webb, D. Giles, and D. Hewitt. Malignant disease in childhood and diagnostic irradiation in utero. Lancet 2:447 (September 1, 1956). 21 ''E i } E E i ''ROUTINE HOSPITAL ADMISSION CHEST X-RAY EXAMINATIONS RATIONALE Written justification for the widespread practice of administering routine hospital admission chest radiographs is difficult to find. However, the assumption is made that the practice is designed to detect clinically silent diseases that might threaten the patient and/or those with whom the patient comes in contact during hospitalization. Carcinoma of the lung is an example of a disease in the former category while tuberculosis is a representative of the latter category. A number of studies have indicated that routine screening for such diseases, even in selected populations considered to be at high risk for development of the disease, yields an insufficient number of positive cases to justify continued screening (2-4). Thus, it is probable that the screening of less selected populations would, if anything, have a lower yield. The Chest X-ray Panel recognized the theoretical possibility that populations selected solely on the basis of diseases requiring admission to the hospital might differ in some way from those populations previously sereened and found to have a low diagnostie yield. However, it was concluded that patients entering the hospital represented such a diverse spectrum of diseases that the chances of their having a higher yield of diseases such as lung cancer, tuberculosis, etc., solely as a result of their being admitted to a hospital, was very remote. It was also fully recognized that even if routine admission films were no longer required, many, if not most, patients admitted to hospitals would still have ac. est x- ray examination as part of the evaluation of the disease process for which they were admitted. However, such an examination should be obtained because of an appropriate clinical history, physical examination, or laboratory test. A patient should not be required to have a chest radiograph solely as a matter of routine administrative protocol. It is anticipated that patients admitted to hospitals for a variety of conditions such as "minor" surgical procedures, various orthopedie procedures, and many conditions common to pediatric and obstetric/gynecologie services would thus be spared administrative:y mandated radiographic examinations. A similar position was stated by the American College of Physicians in 1978 when that organization recommended that a chest x-ray examination (included among several common diagnostic tests), should not be required as a routine procedure for patients admitted to a hospital (1). The recommendation to eliminate routine hospital admission chest radiography conforms to the Chest X-ray Panel's basie contention that any radiographic examination should be justified by the patient's medical condition rather than by administrative mandate. 23 ''REFERRAL CRITERIA STATEMENT FOR ROUTINE HOSPITAL ADMISSION CHEST X-RAY EXAMINATIONS The rationale for obtaining routine chest radiographs of patients admitted to hospitals is to discover unsuspected disease which might directly threaten the health of the patient and/or jeopardize the health of those coming in contact with the patient. However, available literature suggests that the yield of clinically significant information (not available from history, physical examination, or previous diagnostic testing) from such routine screening chest radiographs is low. IT IS THEREFORE RECOMMENDED THAT ROUTINE CHEST RADIOGRAPHS NOT BE REQUIRED SOLELY BECAUSE OF HOSPITAL ADMISSION. This recommendation should not be construed as precluding or advising against the ordering of chest x-ray examinations (1) on the basis of history, physical examination, or specific diagnostic testing, or (2) in selected patient populations in which a significant yield has been previously substantiated or is considered highly likely pending appropriate substantiation. 24 ''oe i a 3. References American College of Physicians reeommendations to the National Blue Cross and Blue Shield Association's Medical Necessity Project. American College of Physicians Policy Statement (April 1978). Feingold, A.O. Routine chest roentgenograms on hospital admission do not discover tuberculosis. Southern Med J 70:579-580 (1977). Routine Chest Radiographs In Hospitals (Editorial). Br Med J 1(5958):592-593 (March 15, 1975). Sagel, S.S., R.G. Evens, J.V. Forrest, and R.T. Bramson. Efficacy of routine screening and lateral chest radiographs in a hospital-based population. N Engl J Med 291:1001-1004 (1974). 25 ''''CHEST X-RAY EXAMINATIONS FOR TUBERCULOSIS DETECTION AND CONTROL RATIONALE More than one hundred years after the discovery of the tubercle bacillus by Robert Koch, tuberculosis is still a major disease in the world. But in the United States, cases and case rates have declined. New cases continue to be found, but most often in urban areas, with increasing numbers prevalent among recent immigrants. Until 1972, the use of diagnostic x-ray screening was the unquestioned detection tool for the diagnosis of tuberculosis. Prior to that time, it was felt that properly conducted x-ray screening, including follow-up of the positive finding, would lead to prompt diagnosis and treatment. In New York City, for example, x-ray screening was widely conducted. The New York City Health Department code required screening of pregnant women, all persons working in maternity and newborn services, all food preparation employees, Parks Department employees, Board of Education employees, as well as persons contacting newly diagnosed tuberculosis patients. In addition, the Lung Association's mobile buses travelled actively among communities offering free mass x-ray screening of the population. But the productivity of these examinations was later found to be extremely low. Most of the persons screened were asymptomatic and latent disease was very rarely detected. In 1972, the Food and Drug Administration's Bureau of Radiological Health issued a statement in cooperation with the Center for Disease Control, the American College of Chest Physicians, and the American College of Radiology recommending that community chest x-ray surveys among the general population not be used as a screening procedure for the detection of tuberculosis, other pulmonary disorders, and heart disease. The American Thoracic Society reeommended that chest x rays not be done as routine screening because the number of tuberculosis cases found is extremely small and these cases would come to medical attention by other methods (a careful history of symptoms, use of tuberculin skin test, and careful followup of people who have the disease). In 1974, the Ninth World Health Organization Committee on Tuberculosis concluded that radiography is an expensive screening procedure for tuberculosis, contributing only a small proportion of the cases discovered and having no significant effect on the subsequent occurrence of cases. Part of the basis for these recommendations was the recognition that tuberculosis is a two-stage disease. The first stage consists of infection by the tubercle bacillus. This infection is a subclinical event that is contained by body defenses in approximately 90 to 95 percent of the cases. In the remaining five to ten percent, the disease may become manifest sometime during their life. The tuberculin skin test can detect tuberculosis in the preclinical stage, and then, utilizing known risk factors, therapeutic measures can be taken to protect against the development of manifest disease. The second stage consists of clinically manifest tuberculosis, a condition that almost always is suggested by symptoms or other epidemiologic factors. The chest x-ray examination is limited in that it can only demonstrate clinically manifest tuberculosis. Recognizing this limitation and the low prevalence of tuberculosis, the Chest X-ray Panel has recommended against routine x-ray screening for tuberculosis detection and control in five specific areas. 27 ''REFERRAL CRITERIA STATEMENT FOR CHEST X-RAY EXAMINATIONS FOR TUBERCULOSIS DETECTION AND CONTROL A chest x-ray examination should always be obtained whenever a specific medical indication exists (e.g., relevant history, symptoms and/or significant tuberculin skin test reaction). However, there are several situations where x-ray examinations have traditionally been performed solely because of administrative mandate, protocol, or by routine. The yield of tuberculosis cases found by screening or repeated chest x-ray examinations has not been shown to be of sufficient clinical value or productivity to justify the inconvenience to the subject, the monetary cost or added radiation exposure. Chest X-Ray Examinations for Employment Mandated chest x-ray examinations, as a condition of initial or continued employment, have not been shown to be of sufficient productivity to justify their continued use for tuberculosis detection (5). Chest X-Ray Examinations in Long-Term Care Facilities Because conventional tuberculin skin testing may not be a reliable screening method in older and/or chronically ill persons and because these individuals may | be at high risk of having tuberculosis, the results of a recent chest x-ray examination should be obtained by the facility (10,12,13). Only if unavailable, a chest x-ray examination should be performed on admission. In the absence of clinical symptoms, repeated chest x-ray examinations have not been shown to be _of sufficient clinical value or productivity to justify their continued use. Repeated Chest X-Ray Examinations of Tuberculin Reactors After an initial evaluation, which should include a chest x-ray examination, repeated chest x-ray examinations of individuals with significant tuberculin reactions, (without current disease), whether or not they have been treated with isoniazid, have not been shown to be of sufficient clinical value to justify their continued use (2,3). Routine Followup of Tuberculosis Patients Who Have Completed Treatment Repeated chest x-ray examinations of asymptomatic tuberculosis patients who have completed treatment have been shown to be of insufficient clinical value or productivity to justify their continued use (4,7,8,9,11). ~ Routine Periodie Chest X-Ray Examinations During Tuberculosis Treatment Radiographic stability does not necessarily indicate success or failure of chemotherapy as reliably as the results of sputum smear and eulture, and assessment of symptoms and clinical status (1,6). However, an occasional x-ray examination may have value in confirming bacteriologic and clinical findings and enhancing patient compliance. 28 ''4, 5. 10. 11. 12. 13. References Albert, R.K., M. Iseman, J.A. Sbarbaro, A. Stage, and D.J. Pierson. Monitoring patients with tuberculosis for failure during and after treatment. Am Rev Respir Dis 114:1051-1060 (1976). American Thoracic Society. Diagnostic standards and classification of tuberculosis and other mycobacterial diseases (14th Edition). Am Rev Respir Dis 123:343-358 (1981). Bailey, W.C., C.A. Sellers, S.O. Lantz, and G.E. Hardy, Jr. Chest radiography during isoniazid therapy. Am Rev Respir Dis 115:877-878 (1977). Bailey, W.C., D.H. Thompson, S. Jacobs, M. Ziskind, and H.B. Greenberg. Evaluating the need for periodic recall and re-examination of patients with inactive pulmonary tuberculosis. Am Rev Respir Dis 107:854-857 (1973). Barrett-Conner, E. The periodic chest roentgenogram for the control of tuberculosis in health care personnel. Am Rev Respir Dis 122:153-155 (1980). Crofton, J. Failure in the treatment of pulmonary tuberculosis: Potential causes and their avoidance. Bull of the IUAT 55:93-99 (1980). Edsall, J. and G. Collins. Routine follow-up of inactive tuberculosis: A practice to be abandoned. Am Rev Respir Dis 107:851-853 (1973). Recommendations for health department supervision of tuberculosis patients. Morbidity and Mortality Weekly Report 23:8 (February 23, 1974). Reichman, L.B. Routine follow-up of inactive tuberculosis: A practice that has been abandoned. Am Rev Respir Dis 108:1442-1443 (1973). ® Stead, W.W. Epidemic of tuberculosis among elderly residents of a nursing home. Am Rev Respir Dis 121 (No. 4, Part 2 of 2 parts):462 (1980). Stead, W.W. and G.H. Jurgens. Productivity of prolonged follow-up after chemotherapy for tuberculosis. Am Rev Respir Dis 108:314-320 (1973). Tuberculosis - North Dakota. Morbidity and Mortality Weekly Report 27:523-525 (1979). Tuberculosis in a nursing home - Oklahoma. Report 29:465-467 (1980). Morbidity and Mortality Weekly 29 ''''CHEST X-RAY EXAMINATIONS IN OCCUPATIONAL MEDICINE RATIONALE The chest x-ray examination is one of the most frequently performed routine procedures in occupational medicine, yet there are almost no published data on its value in that setting (5,8). The examination is used in industry as one of the parameters in evaluating the health of job applicants, in assuring appropriate work placement, in screening persons who work with pulmonary irritants or carcinogens, and in periodic health appraisals unrelated to work exposures, For some purposes in industry, a routine chest x-ray examination is indeed warranted. For others, however, its usefulness may be viewed with uncertainty. Studies among nonoccupational groups have demonstrated that routine chest x-ray examinations that are not based on history, physical examination, and diagnostic testing, cannot be justified in unselected, asymptomatic persons (1,3,4,7). If this is so, then periodic chest x-ray examinations in industry, unrelated to job exposure, should also be done selectively, and based on the same criteria (6). The role of chest x-ray examination for preplacement purposes in industry is controversial. Some believe it should be done selectively based on pertinent data in the occupational and medical history, physical examination, and proposed work assignment. Others believe it should be continued as a routine screening procedure for all applicants. The proponents of the latter position argue that all possible future work assignments within a particular employment are not known at the time of the preplacement examination. They believe strongly in the value of the initial examination as a baseline reference study that may be useful in future health appraisal of the employee. Unfortunately, neither position can be supported by published studies and the dilemma remains unsolved (2). Although background material on which to make a decision is largely unavailable in occupational medicine literature, the Panel recommends that industrial medical departments critically evaluate the current use of routine chest x-ray examination programs in their companies. 31 ''REFERRAL CRITERIA STATEMENT FOR CHEST X-RAY EXAMINATIONS IN OCCUPATIONAL MEDICINE PREPLACEMENT EXAMINATIONS FOR APPROPRIATE JOB PLACEMENT Preplacement chest x-ray examinations should be done selectively based on pertinent factors in the (1) occupational and medical history, (2) clinical examinations and (3) proposed work assignment. JOB EXPOSURE SURVEILLANCE Chest x-ray surveillance of persons who work with or may be exposed to substances that adversely affect pulmonary function or cause pulmonary disease should be based on a periodicity consistent with the current understanding of the disease process. PERIODIC EXAMINATIONS UNRELATED TO JOB EXPOSURE The yield of unsuspected disease (e.g., lung cancer, heart disease, and tuberculosis) found by periodic chest x-ray examinations of unselected populations, not based on history, physical examination, or specific diagnostic testing has been shown to be of insufficient clinical value to justify the monetary cost, added radiation exposure, and subject inconvenience of the examination. It is therefore reeommended that such routine examinations be discontinued. This statement does not preclude chest x-ray examinations based on individual history, physical examination, or specific diagnostic testing (e.g., sputum cytology, electrocardiography, and skin test); or in selected populations shown to have significant yields of previously undiagnosed disease. 32 ''References Abrams, H.L. The "“overutilization" of x-rays. N Engl J Med 300:1213-1216 (May 24, 1979). Ashenburg, N.J. Routine chest x-ray examinations in occupational medicine. JOM 24:18-20 (January 1982). Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J 121:1193-1254 (1979). Dales, L.G., G.D. Friedman, and M.F. Collen. Evaluating periodic multiphasie health checkups: A controlled trial. J Chron Dis 32:385-404 (1979). Douglass, B.E. Examining healthy patients: How and how often? Mayo Clin Proce 56:57-60 (1981). Guidelines ‘for use of routine x-ray examinations in occupational medicine: Committee report. JOM 21:500-502 (July 1979). Periodic health exams in perspective. The Harvard Medical School Health Letter 5:3-4 (1980). Spitzer, W.O. and B.P. Brown. Unanswered questions about the periodic health examination. Ann Intern Med 83:257-263 (1975). 33 ''APPENDIX A CONSULTANTS TO THE CHEST X-RAY PANEL Lloyd Cloud, D.D.S. Health Standard and Quality Bureau Health Care Financing Administration Department of Health and Human Services Washington, D.C. H. Barrie Fairley, M.D. Vice Chairman, Department of Anesthesia San Francisco General Hospital San Francisco, California Cornelius R. Foley Commonwealth Institute of Medicine, Inc. Boston, Massachusetts Stephen Levin, M.D. Health, Safety and Environment Industrial Union Department AFL-CIO Washington, D.C. Thomas A. Lincoln, M.D. American Occupational Medical Association New York, New York 34 Otha W. Linton American College of Radiology Washington, D.C. David Logan, M.D. Directorate of Technical Support Occupational Safety and Health Administration Baltimore, Maryland Darrell K. Mattheis Organization Resources Counselors, Inc. Washington, D.C. Robert D. Moseley, Jr., M.D. Chairman, Department of Radiology University of New Mexico Albuquerque, New Mexico E. Andrew Neal, M.D. Chief, Gastroenterology Kaiser Medical Center Santa Clara, California ''APPENDIX B ANNOUNCEMENTS OF THE DRAFT CHEST X-RAY REFERRAL CRITERIA PANEL REPORT Bureau of Radiological Health Bulletin MDDI Reports "The Gray Sheet" Diagnostie Imaging Federal Register PSRO Reports Washington Actions on Health Devices and Diagnostics Letter Product Safety and Liability Reporter American Occupational Medical Assoc. Report Family Practice News Internal Medicine News March 1981 March 1981 May 1981 June 1981 June 1981 June 1981 June 1981 June 1981 July/Aug 1981 September 1, 1981 September 1, 1981 CATEGORIES OF REQUESTS FOR THE CHEST X-RAY REFERRAL CRITERIA PANEL REPORT Category Hospitals and Clinics Industry Government International Requests Third Party Reimbursers/Health Planners Individual and Private Practices Colleges and Universities Occupational Health/Medical Consultants Journals/Medical Publications Professional (Medical) Specialty Groups Other TOTAL 35 Requests 226 141 119 41 38 36 34 16 12 10 9 682 ''APPENDIX C PROFESSIONAL ORGANIZATION REVIEWERS American Academy of Family Physicians American Academy of Occupational Medicine American Academy of Pediatrics American College of Chest Physicians American College of Chest Surgeons American College of Osteopathic Internists American College of Physicians American College of Preventive Medicine American College of Radiology American College of Surgeons American Lung Association American Occupational Medical Association American Osteopathic Association American Osteopathic College of Radiology American Public Health Association American Society of Internal Medicine American Thoracic Society Conference of State and Territorial Epidemiologists State and Big City Tuberculosis Controllers 36 ''American Thoracic Society APPENDIX D MEDICAL SECTION OF THE AMERICAN LUNG ASSOCIATION CONTROL OF TUBERCULOSIS THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY WAS ADOPTED BY THE ATS BOARD OF DrrREcTorS, MARCH, 1983. THIS Is A JOINT STATEMENT OF THE AMERICAN THORACIC SOCIETY AND THE CENTERS FOR DISEASE CONTROL. Tuberculosis Control Objectives The objectives of tuberculosis control relate to individuals as well as the public. For in- dividuals, the objectives are to eliminate death and to decrease and eliminate disabil- ity, illness, emotional trauma, family dis- ruption, and social stigma. For the public, the objectives are to interrupt and prevent transmission of tubercle bacilli. The ulti- mate goal is the eradication of tuberculosis in the United States. Tuberculosis control is based on the prin- ciples of surveillance and containment. Sur- veillance is concerned mainly with activities related to finding cases and guiding them into the health care system, learning about the existence of cases already in the system, and tracking cases. Containment is con- cerned mainly with treatment and preven- tion activities. Surveillance Surveillance is necessary to accumulate epi- demiologic data on disease frequency, its demographic and geographic distribution in the community, and its trends. This in- formation is necessary to plan diagnostic and treatment services which are available and accessible to all patients, and to protect the community through containment activ- ities which assure that transmission is stopped. The 2 components of tuberculosis surveillance are (/) finding the cases, and (2) knowing about the cases that have been found. Many persons with tuberculosis are iden- tified because they seek medical care for symptoms caused by the disease. In addi- tion, persons already receiving health care for another condition may be found to have concurrent tuberculosis. Thus, patients themselves and providers of primary health care are among the most important finders of tuberculosis. People must be taught to recognize symptoms of potential disease and to seek medical care when these symp- toms occur and persist. Health providers must be alert to the possibility of tubercu- losis. In the course of examination for other health problems, tuberculous disease and infection can be found. Screening Fewer tuberculosis cases are identified through screening activities than by self- referral. Tuberculosis screening has been thoroughly evaluated, and its methods, limitations, and indications well estab- lished. Effective screening tools are avail- able for detecting both those with tubercu- lous disease and those at risk of developing disease because of prior infection with M. tuberculosis. Disease implies the presence of symptoms consistent with tuberculosis, clinical findings consistent with tuberculo- sis, or both. Infection is indicated by a sig- nificant reaction to the tuberculin skin test in the absence of symptoms or findings sug- gesting disease. Extremely effective drug regimens are available for treating patients with disease and for preventing disease in infected individuals. The purpose of screening for tuberculosis is to find potential transmitters so that transmission of tuberculous infection can be prevented. The purpose of screening for tuberculous infection is to find persons at risk so that progression of infection to dis- ease can be prevented. In tuberculosis con- trol programs, screening should be given much lower priority than management of patients and contacts. Mass radiography of the general population, once common- place, no longer has a role as a screening procedure. More recently, screening for tuberculosis has relied upon the tuberculin skin test, and the emphasis in screening has shifted to finding those who are at risk of developing disease and infecting others as well as detecting those who already have disease. The tuberculin skin test is the preferred initial method of screening. A careful his- tory, ana attention to signs and symptoms suggestive of tuberculosis, are important screening methods in all instances. Among groups with a high prevalence of infection, or anergy to tuberculin, or both (e.g., el- derly patients in nursing homes), tuberculin skin tests and chest radiographs both may be indicated for initial screening. Before screening programs are started, services should be available for appropriate follow- oa Reprinted by permission of the American Thoracic Society 37 up, including chemotherapy to completion _ for the prevention and treatment of disease. SCREENING OF POPULATIONS Mass screening of the general population for tuberculosis has become an inefficient method of finding infection and disease. Moreover, routine screening of certain sub- populations, such as all children entering school, has, in general, been abandoned because infection rates have reached such a low level. In selected subpopulations, in whom infection rates are not low, screening is warranted. Continuous evaluation is necessary to determine if a screening program is effi- cient and effective in reducing disease and infection rates. As rates decrease, a point will be reached where continued screening is no longer indicated. To determine whether or not screening of a subpopulation is indicated, data on dis- ease incidence, age-specific rates of infec- tion, and the impact of control measures on the target population should be reviewed. Groups experiencing a disease rate in excess of that for the U.S. general population or in which the rate of infection among chil- dren less than 5 years of age is greater than 1% should be considered for screening. Included in this category are persons com- ing to the U.S. from countries with high rates of tuberculosis, e.g., countries of Asia and Latin America. Such persons constitute a significant reservoir of potential disease. Settings in which such screening would be appropriate include school and pre-employ- ment health examinations and at time of entry into the medical care system (e.g., physician’s office or out-patient clinic). SCREENING IN INSTITUTIONS Screening for tuberculosis in institutions involves the detection of disease and new infection in settings where transmission of tuberculosis is likely (e.g., health care facil- ities and correctional institutions) or where the presence of an individual with disease Reprints may be requested from your state and local Lung Association. ''AMERICAN THORACIC SOCIETY MEDICAL HISTORY PHYSICAL EXAMINATION History to exposure to tuberculosis, from high-prevalence population, or high-risk medical condition Tuberculin Skin Test Significant Reaction to Reaction Skin Test to Skin Test Not Significant No Further Evaluation” ieee Normal Abnormal INH Further Preventive Evaluation Therapy if under age 35 or if addi- tional risk rent factors present Indicated | Signs and/or Symptoms consistent with Tuberculosis Chest X-Ray and Tuberculin Test Normal Abnormal Chest X-ray Chest X-ray Skin Test Significant or Significant Reaction to Not Significant Reaction Skin Test to Skin Test Not Significant INH No Further Preventive Evaluation Therapy if under age 35 or if Therapy additional as risk factors Indicated present Fig. 1. Patients in acute care health facilities (general and psychiatric hospitals). * Chest X-ray may be taken if indicated for evaluation of other medical conditions if reaction to tubercu- lin skin test is not significant. would pose a particular hazard to others (e.g., child care facilities and newborn nur- series). Included among health care facili- ties are general hospitals, psychiatric hospi- tals (figure 1), chronic disease hospitals, long-term health care facilities, resident care facilities, and any other specialized pa- tient care facilities (figure 2). Correctional institutions include facilities for both short- term and long-term detention (figure 3). Child care facilities include nurseries, day care centers, boarding schools, develop- ment centers for the mentally retarded, ju- venile detention centers, and other resident care facilities for children and youth. When within an institutional population (including personnel) one or more of the following conditions exist, screening is rec- ommended: (/) The population has a high prevalence of tuberculous disease. (2) The population has a high prevalence of tuber- culous infection and is at risk of developing disease. (3) The persons are in an environ- ment in which there is high risk of transmis- sion of tuberculous infection, that is, of be- coming infected. (4) The persons, although not at high risk of tuberculosis, should they develop disease have the potential of infect- ing young children or persons with sup- pressed immune response. One or more of these conditions may apply to the types of institutions mentioned above. The particular type of screening program to be recommended depends upon the like- lihood of exposure (e.g., the likelihood that a patient with unsuspected tuberculosis is admitted to a general ward in an acute care hospital), the possibility of transmission of tuberculosis (e.g., number of susceptibles, the duration of exposure, the degree of crowding and adequacy of ventilation sys- tems), and the hazard posed to others by inadvertent exposure to tuberculosis (e.g., the increased susceptibility to tuberculo- sis of neonates and immunosuppressed patients). To determine the type of screening pro- gram suitable for a given institution, longi- tudinal data on the incidence and preva- lence of tuberculous disease and infection in both personnel and persons served by the institution and in the local community should be available. These data are essen- tial to evaluate the effectiveness of the screening program and to determine if and 337 when modifications in the screening pro- gram should be made. SCREENING OF PERSONNEL Initial screening test. All personnel should receive a tuberculin skin test before em- ployment unless they have a documented medical record of a significant tuberculin skin test reaction. Those without a signifi- cant reaction can be retested within 1 to 2 weeks to identify those who demonstrate “boosting” following the second test and to avoid the possibility that such individuals would be considered “recent converters” on subsequent testing. This two-step proce- dure is most important for use in areas of the country where there is a high prevalence of nontuberculous mycobacterial disease as it is these organisms that are most likely to be responsible for the boosting. In other locations, institutions should develop base- line data to determine the level of boosting occuring within their population. Decisions concerning the use of the two-step proce- dure in these institutions should be based on this data. Those with a significant tuber- culin test reaction should receive a chest radiograph and be evaluated for chemo- therapy. Personnel should be provided with a record of results of skin tests and chest radiographs to avoid repeat testing should they change employment. Repeat screening of personnel with signifi- cant reactions. Persons with known signif- icant reactions to tuberculin have no need for additional tuberculin tests or radio- graphs but should be instructed to report promptly any symptoms suggesting tuber- culosis. Institutions should exercise caution in placing untreated infected individuals in MEDICAL HISTORY PHYSICAL EXAMINATION [ Patients under age 65 No high-risk medical conditions Tuberculin Skin Test Not Significant Significant Repeat Skin Test Not Significant Abnormal! Normal Significant No Further Evaluation Therapy as Indicated Patients 65 years or older; those with high-risk medical conditions or signs/ symptoms consistent with tuberculosis regardiess of age Chest X-Ray and Tuberculin Test Normal Abnormal Chest X-ray Chest X-ray Skin Test Significant or Significant Reaction to Not Significant Reaction Skin Test to Skin Test Not Significant | Further Repeat Evaluation Skin b INA Test Preventive Therapy if high Therapy risk medical con- as dition present or Significant Not Indicated if under age 35. Significant Otherwise observe for signs and symptoms of disease No Further eee | Fig. 2. Patients in extended care health facilities (long-term health care and residential facilities; nursing homes). 38 '' 338 MEDICAL HISTORY, PHYSICAL EXAMINATION TUBERCULIN TEST AND CHEST X-RAY Abnormal Chest X-ray Skin Test Significant or Not Significant Further Evaluation Therapy as Indicated Normal Chest X-ray Significant Reaction to Reaction Skin Test to Skin Test Not Significant INH No Further Preventive Evaluation Therapy as indicated, observe for signs and symptoms of disease Fig. 3. Inmates in institutions, medium or long-term detention (1 week or longer). areas such as neonatal or oncology units or in schools or child care centers where expo- sure to tuberculosis poses a special hazard to those served in the institution. Repeat screening of personnel who are non- reactors. The need for periodic repeat tu- berculin testing should be determined by the risk of acquiring a new infection. It should be based on consideration of the fol- lowing factors: (/) the number and location of persons with tuberculosis admitted to the institution (to determine the risk of occupa- tional exposure), (2) the number and loca- tion of tuberculosis patients in the com- munity (to determine the risk of exposure in the community), (3) the number of person- nel already infected who have not com- pleted drug therapy (to determine number of personnel at risk of developing disease and infecting others in the institution), (4) the number of personnel who become new- ly infected (to determine the risk of becom- ing infected in the institution and in the community), and (5) the pattern of air flow throughout the institution (to determine the possibility of airborne transmission of in- fection from one area of the institution to another). For instance, in a hospital rarely admit- ting patients with tuberculosis and serving a community with an extremely low preva- lence of tuberculous infection annual skin testing may not be indicated. On the other hand, an acute care hospital serving a pop- ulation with a high disease rate and oc- casionally admitting patients with unsus- pected tuberculosis should have an ongoing screening program with periodic skin test- ing of employees at risk of exposure no less than at 12-month intervals. SCREENING OF PERSONS SERVED BY INSTITUTIONS Programs to screen the persons who are served by the institutions will vary. In addi- tion to the principles stated previously, there are several other considerations. Tu- berculosis transmission is a greater risk in institutions where persons remain for long periods of time. Opportunities for exposure are increased because neither potential source cases nor susceptible contacts are likely to be quickly removed from the envi- ronment. Initial screening of persons enter- ing such institutions can be important in preventing inadvertent introduction of tu- berculosis into a risky setting. For patients, nursing home residents, and prisoners, such factors as age, general state of health, and time spent at the institution (hours per day and number of days or months) all enter into the design of the screening program. Contact Investigation Contacts of newly diagnosed cases are the most easily identified high-risk group. Ex- amination of contacts is one of the most important methods of finding persons with disease or with infection. The risk to con- tacts is related to various features of the source case, the contact, and the environ- ment that they share. Many factors interact to influence the transmission of infectious particles (droplet nuclei) from the source case to the contact. IDENTIFICATION OF SOURCE CASE As soon as the diagnosis is reasonably es- tablished on laboratory and/or clinical bases, investigation of contacts should commence. There should be no waiting for positive cultures if history, sputum smears, and chest radiographs are suggestive of tu- _berculosis. DEVELOPMENT OF TRANSMISSION PROBABILITY DATA When a source case has been identified, the appropriate procedure in contact investiga- tion entails the development of a data base, evaluating each of the factors noted below. These data are usually gathered by inter- viewing the source case and reviewing re- lated historic and laboratory records. It may also be necessary to visit the source case’s home or place of employment to as- semble a satisfactory initial data base. Source case characteristics. Any person who is capable of generating aerosolized particles containing tubercle bacilli from his or her respiratory tract is a potential transmitter of infection. Factors that indi- 39 AMERICAN THORACIC: SOCIETY cate the probability of disseminating tuber- culous infection are as follows: (/) If the source case is not receiving adequate antitu- berculosis chemotherapy, the probability of his or her producing infectious particles is significantly enhanced. (2) The presence of acid-fast bacilli in the appropriately exam- ined sputum smear is indicative of a greater infectious potential. (3) The ability to cul- ture Mycobacterium tuberculosis from se- cretions of the source case is in itself less important quantitatively as an indicator than is the positive sputum smear. (4) The presence of cavitation in the chest radio- graph is a presumptive indication of signifi- cant communicability. (5) The presence of tuberculous laryngitis also increases infec- tiousness. (6) The presence of cough in- creases the probability of aerosol genera- tion. (7) The unwillingness or inability of the source case to cover his or her cough also may be assumed to increase the risk of communicating the infection. (8) The vol- ume and viscosity of respiratory secretions also influence the chance of producing in- fectious particles, with high volume and watery sputum being regarded as risk fac- tors. (9) Forceful exhalational maneuvers, such as singing or shouting, may increase the chance of producing infectious parti- cles. (10) Prolonged duration of respiratory symptoms may augment the likelihood of transmission of infection. Environmental air factors. The air is the vehicle by which the infectious particle or droplet nucleus is transported from the source case to susceptible persons. The greater the concentration of these droplet nuclei in the air shared by the source case and his or her associates, the greater the risk of these contacts. The following fac- tors alter the concentration of infectious particles in the air. (7) The volume of air common to the source case and contact is critical. If low, the concentration of infec- tious particles is increased, e.g., in sharing a small room. (2) Ventilation will dilute the concentration of potentially infectious par- ticles. (3) Recirculation of air may result in the accumulation or concentration of infec- tious particles because droplet nuclei re- main suspended in the air, e.g., ‘ships, hos- pitals, and other structures with closed- circuit heating and air-conditioning sys- tems. (4) Filtration of air by a system effi- cient enough to entrap the droplet nuclei may remove them from recirculated air. (5) Ultraviolet irradiation of the air within the shared space may reduce its infectious potential by killing the tubercle bacilli that are suspended within the droplet nuclei. Contact risk factors. All persons who have recently shared air with the source case may be seen as potentially infected contacts. The following are factors that are known to modify the risk of infection for these per- sons. (/) Increased time in association with the source case influences the probability of infection; members of the source case’s ''AMERICAN THORACIC SOCIETY household would be examples of prolonged exposure, although this is not necessarily so. (2) Physical proximity to the source case by the contact may also influence the likeli- hood of infection; although the droplet nu- clei eventually undergo random distribu- tion within the shared air space, there is some evidence that sustained physical close- ness within the air environment may result in increased risk for contacts. (3) Antitu- berculosis chemotherapy taken by the con- tact at the time of exposure reduces the in- fection risk, an example of true prophy- laxis. (4) Prior infection with tuberculosis, as indicated by a significant skin test reac- tion before exposure to the indentified source case, reduces risk. STRUCTURING OF INVESTIGATIONAL PROGRAM Once these data have been assembled, two important judgments that influence the conduct of the contact investigation are es- tablishing the priority by source case and classifying the contacts of each source case. Establishment of investigational priorities. The estimated probability of transmission should influence the priority, rapidity, and thoroughness with which contact investiga- tion is conducted. By using this systematic approach, appropriate and productive pub- lic health programs can be carried out. Classification of contacts. For each source case, contact investigation should proceed in an orderly manner, starting with those who are most likely to have been infected. There are no uniform definitions of con- tacts. Members of the immediate family or others who have shared accommodations with the source case in the recent past usually have been labeled household con- tacts. Contacts in working, leisure, or other settings have been designated by other terms such as “close,” “intimate,” or “cas- ual.” The most important consideration in contact investigation is the probability of infection in a contact. Therefore, the first step is simply to allocate contacts into higher and lower risk contacts. A higher risk contact would be any per- son who shared the environment air with a source case for a relatively longer time and who has other risk factors relatively higher than other known contacts. Thus, the mem- bers of the immediate family would prob- ably fall within this category; also included would be work or leisure contacts who might have exposure comparable to house- hold members. Applying the various transmission risk factor data to persons known to have asso- ciated with the source case, it is apparent that certain of these contacts have a lesser probability of having been infected. Al- though possible, it is unusual for tubercu- lous infection to be transmitted during a brief exposure to a relatively small number of aerosolized particles. ESTABLISHING LIMITS FOR INVESTIGATION By initially evaluating the higher risk con- tacts for evidence of tuberculous infection and/or disease, the actual infectiousness of the source case can be inferred. The following are guidelines for limiting the extent of a contact investigation. (/) Evaluate all contacts who present them- selves and request study; such persons can- not be turned away. (2) Initiate investiga- tion with higher risk contacts; if there is no evidence of recent transmission of infection within this group, it is appropriate not to extend the investigation. (3) If data suggest recent infection within the higher risk group, the limits of investigation should be extended progressively through the lower risk contacts. To ensure that the investiga- tion has identified the significant bulk of infections that might be attributed to the source case, progressively lower risk con- tacts would be evaluated until the level of infection detected approximates the levels of infection within the local community. (4) At each stage of the investigation, establish the number and identity of contacts to be examined. Establishing such a denominator helps to assure that no contact who needs to be examined is missed. Containment Containment means stopping the spread of infection and disease. The primary methods of containment are: (/) chemotherapy properly prescribed for persons with dis- ease and taken as prescribed; (2) preventive treatment of persons exposed to tuberculo- sis (contacts); and (3) preventive treatment of other infected persons, all of whom must have been contacts at one time and are at some risk of developing disease. With adequate chemotherapy, almost all patients will become bacteriologically nega- tive, recover, and remain well. Retreatment regimens, -when necessary, are generally more complicated, more toxic, and more expensive, but nevertheless successful. Even for retreatment of tuberculosis, the need for surgery has almost vanished. Drugs, dosages, combinations, adverse re- actions, and tests for adverse reactions have been detailed in other publications. Current therapeutic regimens permit the design of a treatment plan tailored to each patient’s needs. Because most treatment failures are due to irregularity or interrup- tion of self-medication, every effort should be made to deliver care in ways that assure continuity of treatment and completion of the prescribed drug regimen. By under- standing the patient’s lifestyle and allowing flexibility in the way treatment is provided, it is possible to devise programs that facili- tate patient participation and completion of therapy. Alternatives to self-medication, such as directly administered treatment on a-daily or intermittent basis, are necessary for patients who cannot or will not take medication by themselves. 49 339 Preventive therapy of persons in high- risk groups is essential to achieve the goal of eradication. It is particularly important to give preventive therapy to persons in close contact with recently diagnosed cases of tuberculosis. In the United States, because of the very low rate of infection, vaccination with ba- cillus Calmette-Guerin (BCG) has only limited use. Cases HOSPITALIZATION Many tuberculosis patients do not require hospitalization; the diagnostic process and subsequent management are accomplished entirely on an ambulatory basis. Patients who are very sick, whose diagnosis presents difficulties, or whose management is com- plicated by other problems (such as drug resistance) may receive some portion of their care in a hospital, ordinarily a com- munity general hospital. The period of hos- pitalization is usually short, after which the care is continued on an ambulatory basis. The few patients who may require pro- longed institutional care, generally for problems other than their tuberculosis, can be managed in nonspecialized intermediate or long-term facilities where tuberculosis treatment is continued. Isolation is not in itself a justification for hospitalization. However, when a patient with tuberculosis needs to be hospitalized, appropriate infection control practices should be followed to protect employees and other patients from infection. The safest place for the patient is at home, on chemotherapy, with contacts receiving pre- ventive treatment. When the patient can resume normal activities depends on the re- sponse to treatment, the nature of the activ- ities, and who will be exposed to him or her in the course of those activities. An exact moment of achieving noninfectiousness is impossible to recognize. Patients differ in this respect, but most infectious patients become noninfectious very rapidly after starting chemotherapy — within several days to a few weeks. Some patients are diag- nosed without ever having become infec- tious. DISCHARGE FROM CARE Before discharge from the treatment pro- gram, patients should be instructed as to what symptoms might be associated with activity of the tuberculous process and of the importance of prompt evaluation of these symptoms. They should also be re- ferred to an appropriate source of continu- ing general health care, making sure that a history of successfully treated pulmonary tuberculosis is transferred to the patient’s medical record. Routine follow-up exami- nations for tuberculosis are unnecessary. Patients who have completed adequate therapy but who, because of coexistent dis- ease (either pulmonary or nonpulmonary, ''340 such as silicosis or Hodgkin’s disease), may be at increased risk of activating or reac- tivating tuberculosis should—as a part of the management of the concurrent dis- ease—have periodic reevaluations for tuberculosis. TREATMENT OF PATIENTS Every effort should be made to assure the success of chemotherapy by concentrating on close patient supervision during the pe- riod of drug-taking. Tuberculosis care is provided by a variety of sources in the com- munity, both private and public, including individual practitioners and institutions. This care is financed by a mixture of third- party payments, tax funds, and private funds. No patient should be denied diag- nostic and treatment services because of inability to pay. Patients can receive care from their usual source with specialist con- sultation when needed. Good laboratory services are essential for the diagnosis and treatment of tuberculosis. Proper identifi- cation of the organism and drug sensitivity testing must be available. Among those completing antituberculous treatment regimens prescribed, more than 95% of patients treated for the first time can be treated successfully. However, this rate of success is rarely attained under pro- gram conditions. A major reason for the discrepancy is that a variable percent of pa- tients fail to take their medications as ad- vised. Unreliable self-administration of many medications, given for a variety of ill- nesses, has been documented world wide. Currently, in some large, urban centers, up to 60% of patients fail to complete the sug- gested duration of treatment. Delivery of antituberculosis treatment includes design- ing programs that can efficiently dispense medication, monitor the response to treat- ment, check for drug toxicity, detect non- compliance and respond to the problems presented by the noncompliant patient. Monitoring treatment response. A persis- tently positive sputum culture is the only sure sign of treatment failure or relapse. Chest radiographs, symptoms, weight loss, and microscopic evaluation of the sputum correlate poorly. Over 90% of patients tak- ing isoniazid (INH) and rifampin (RMP) should become sputum negative within three months of starting treatment. Sputum that remains culture-positive beyond this period should suggest the possibility of drug-resistant organisms or failure to take prescribed drugs. Monitoring drug toxicity. Routinely moni- toring laboratory tests of hepatic function (serum glutamic oxaloacetic transaminase (SGOT), serum biliburin, and alkaline phosphatase) does not necessarily predict drug related hepatic disease in INH recipi- ents. Monthly determination of the SGOT is suggested by some, but there are few data to support this practice. If an SGOT is ob- tained as a routine screen, in conjunction with symptoms suggesting hepatitis, or for a separate reason, and it exceeds three times the normal laboratory value, the decision to continue INH or RMP must be reevalu- ated. Patients receiving INH should be in- structed to report symptoms suggesting hepatitis (fever, anorexia, myalgias, head- ache, malaise, nausea, or jaundice). Pa- tients receiving twice weekly RMP should be regularly monitored by history for possi- ble manifestations of thrombocytopenia (purpura, petechiae, hematuria), or a “flu- like syndrome.” If streptomycin is being used, vertigo, giddiness, and ataxia should be sought, as they will occur and require discontinuation of SM in up to 10% of pa- tients. Monitoring compliance. Demographic vari- ables such as age, sex, race, and marital status do not predict noncompliance; nor do socioeconomic status, occupation, level of income, education, or religious back- ground. The experience of many tuberculo- sis program directors suggests that the sin- gle, unemployed, inner city, male alcoholic is most likely to be noncompliant. Delivery of care must include methods to monitor compliance. Physicians consistently overestimate com- pliance. A number of techniques have been developed to assist in identifying the non- compliant patient. These include urine tests to check for the presence of various medi- cations, serum drug levels, and pill counts. Unless these are performed on a surprise basis, they may be unreliable or reflect compliance over the preceding 12 to 24 hours only. Some physicians have used de- vices that monitor the regularity of pill removal. Under program conditions, most non- compliant patients are discovered by their failure to return for follow-up clinic visits. Having an accurate record system is thus of paramount iniportance. An effective com- munication system is also needed to assure that the discovery of missed appointments comes to the attention of the responsible public health officials. Each patient’s file should contain a full social and family his- tory identifying (7) current addresses of family members, relatives, and friends; (2) anticipated moves; and (3) habitual places of living, eating, drinking, recreation, and employment. This information is needed at the beginning of treatment should noncom- pliance become a problem. Other helpful information may include the response to questions such as “Where should your check be sent?” or “Who should we notify if you die?” If the patient cannot be found using the data present in his/her record, additional information must be sought. The following sources may be helpful in locating a non- compliant patient: (J) post office for for- warding addresses; (2) telephone and city directories; (3) voter registration files; (4) welfare agencies; (5) retail credit agencies; 41 AMERICAN THORACIC SOCIETY (6) motor vehicle bureau; (7) schools (for patients with school-aged children); (8) em- ployment agencies; (9) police, court, and mission records; (/0) Office of Vital Statis- tics; (J/) general hospitals; (/2) Veterans Administration; (J3) trade unions; (/4) neighborhood stores; (/5) city, gas, electric and water company records; and (/6) Im- migration and Naturalization Service. Promoting compliance. Characteristics of the therapeutic regimen are known to affect patient compliance. Shorter durations of therapy, fewer drugs, and reduced frequen- cy of drug administration have been found to improve compliance. It is hoped that a major effect of short course chemotherapy will be to improve patient compliance. For some patients, cooperation with antituber- culous therapy may be greater when an in- jectable medication is used. Tuberculosis programs should be de- signed to minimize patient frustration and default. Methods to do so include (/) re- duction of waiting time by use of individual patient appointments, (2) appointment re- minders by post card or phone call, (3) ex- pansion of services to include evening and weekend hours, (4) establishing treatment facilities in community neighborhoods and the work place, (5) development of per- sonalized transportation services, (6) provi- sion of interpreters and bilingual-bicultural staff, (7) removal of all fees, and (8) assign- ing a specific case worker to the patient so that continuity of care is assured. While all of these methods are generally accepted and potentially will improve compliance, none have been tested in an organized fashion. Forgetfulness may be a major reason for irregular drug ingestion. Some suggest plac- ing medication on a calendar that hangs in a conspicuous place in the patient’s home. Instructing the patient’s family may add an element of supervision. However, patient education is of questionable value, as knowledge about an illness has not been shown to improve compliance with ther- apy. Simplicity of regimen does promote compliance. Directly supervised drug ad- ministration is the only method of assuring patient compliance for the prescribed dura- tion. Because daily supervision is impracti- cal for large number of outpatients, inter- mittent therapy may be preferable. Inter- mittent administration (2 to 3 times per week) of several different regimens of 18- month duration has been proved effective with less than a 10% rate of missed treat- ments. The duration of twice-weekly ther- apy can be as short as 9 months when INH and RMP are used in combination. The di- rect administration of this supervised regi- men may be performed by trained outreach workers who may be less costly than nurses and have proven to be effective. Contacts Once contacts have been identified, addi- tional data should be developed. A diag- ''AMERICAN THORACIC SOCIETY nostic evaluation should be performed, in- cluding medical history, tuberculin skin test, chest radiograph, and if indicated, sputum examination. . Once the contacts have been classified and evaluated, the next step is to recom- mend plans for treatment. All contacts found to have current disease, past disease, or tuberculous infection, should receive appropriate treatment. Even when the ini- tial reaction to a tuberculin skin test is not significant (< 5 mm), a contact should be offered INH preventive therapy, unless contraindicated, when the transmission risk factor data suggest high probability of in- fection, or if evaluation of other contacts with a similar degree of exposure demon- strates high prevalence of infection, i.e., tuberculin reactivity, or if the implications of not treating potentially evolving disease are substantial (e.g., in infants, children < 6 years of age, or persons with impaired im- munity). A repeat tuberculin test should be performed at 10 to 15 weeks; if this is not significant and contact has been broken with the source case, INH may be stopped; if the repeat tuberculin test is significant, a chest roentgenogram should be obtained to exclude disease, and INH should be con- tinued for a full course. If there are contra- indications or if this contact refuses INH, a chest roentgenogram should be recom- mended and a follow-up tuberculin test ob- tained at 6 to 12 weeks. If the repeat tuber- culin tests are not significant, no further evaluation or surveillance is indicated. If the factors noted above (high risk profile, high rates of infection among other con- tacts, or high risk from latent infection) do not pertain to this person, it is recom- mended that no further evaluation or sur- veillance be performed unless further expo- sure is known to occur. Guidelines for Tuberculosis Control Programs Although tuberculosis is both preventable and curable, it continues to be a major pub- lic health problem in many cities and states in the United States. Elimination of this disease will require coordination of efforts of public health agencies, voluntary health associations and medical care providers. The objectives of a community tubercu- losis control program are: 1. All persons with infectious tuberculo- sis will become noninfectious. 2. All persons (contacts) exposed to in- fectious cases will be informed of their ex- posure and receive appropriate medical examinations. 3. All infected contacts and other identi- fied high-risk individuals will be treated so that they will not become infectious. The control of tuberculosis by agencies of government at the state level is mandated by law. Health departments have the legal responsibility to provide effective surveil- lance of tuberculosis, to ensure that con- tainment actions are carried out, and to as- sess program performance. Health depart- ments must receive strong and continuing support from voluntary health organiza- tions and medical care providers if tubercu- losis control objectives are to be achieved. Although the organization of a tuberculosis control program will vary according to the specific needs of each community, all pro- grams must include the following essential components: A. Standard policies, procedures, and guidelines for the community system of sur- veillance, containment, and assessment should be established with input from rep- resentatives of the health department, med- ical practitioners and other health care agencies providing services for persons with tuberculosis. These policies and procedures should be consistent with the recommendations of the American Thoracic Society and Centers for Disease Control. These policies should identify standard practices for the diagnos- tic, treatment and prevention services es- tablished in the community. They should be distributed to all health care providers. Policies should be reviewed annually to as- sure that they remain consistent with cur- rent knowledge. B. Priorities must be established for tuber- culosis control activities. In order to determine priorities, it is first necessary to establish a data base. This should include current demographic data such as the age distribution and ethnic com- position of the population and possible re- cent shifts in population subgroups. It is important to review the current re- ported incidence and prevalence of tubercu- losis in each subgroup within the popula- tion to determine patterns and trends of disease and infection in the community. In- formation from special surveys or epidemi- ologic studies may provide data on the rate of tuberculous infection within special sub- populations. Before priorities can be set, it is necessary to conduct a careful inventory of past accomplishments, as well as failures to meet established standards. Other sub- jects to review include: validity of data, organizational structure and staffing of the tuberculosis control program, qualifica- tions and training of personnel, funding mechanisms and sources, ‘accessibility or duplication of services, current manage- ment strategies, and linkage within the community to other sources of care. During this review process, current (state, munici- pal, or county) legislation and ordinances should be thoroughly evaluated to expunge outdated or inappropriate requirements. C. Effective reporting and record systems should be developed and maintained by the health department. All newly diagnosed cases of tuberculosis must be promptly reported by the physician or other health care practitioner to the 42 341 health department; community laboratories should report positive bacteriology results. To carry out effective assessment, health departments must maintain a record system for up-to-date clinical and therapeutic in- formation on all current tuberculosis cases and suspects in the community. Health care providers must also periodically (at least quarterly) provide the health department with current information on clinical status, chemotherapy and bacteriology. Health departments also need to keep information on the examination and treatment status of contacts, especially those exposed to infec- tious cases. Case registers and contact rec- ords need to be reviewed frequently by re- sponsible health department staff who can initiate appropriate follow-up actions for patients whose records are not up-to-date and who may be public health risks. At least annually, health department staff should assess progress toward achievement of program objectives, and assemble and analyze program management and morbid- ity data. Based on these assessments health departments should annually prepare a “state of tuberculosis in the community” report. D. Each community must establish pro- grams that provide high quality care for persons with tuberculosis or with the poten- tial for developing tuberculosis. Regardless of who provides care for the patient with tuberculosis, the health depart- ment is responsible to ensure the care is available, is of appropriate quality, and is coordinated. Many cases of tuberculosis can and should be treated within the private medical care sector where they receive treat- ment for other health problems. Genera- tion of third party support for tuberculosis services is desirable; however, diagnostic, treatment and prevention services must be available to all persons in need of such care without consideration of the patient’s abil- ity to pay. There should be a statewide sys- tem of tuberculosis laboratory services. All these services should be geographically and temporally available and accessible. Special emphasis should be placed on the appropri- ate use of short-course chemotherapy regi- mens and the use of directly administered daily or intermittent treatment for patients who are unwilling or unable to complete self-administered therapy. Providers of tuberculosis services should follow current recommendations of ATS and CDC for treatment of disease and pre- ventive therapy. Services should be pro- vided by health practitioners who are quali- fied as a result of adequate education and experience in the management of tuberculo- sis. Such practitioners may include physi- cians’ assistants and nurse practitioners in addition to physicians and public health nurses. Outreach activities can often best be performed by other trained employees. When possible, these effective workers should come from the same linguistic cul- ''342 tural, social, and ethnic groups as the pa- tients. There should be an established con- tinuing education program to ensure that providers of care are aware of the current state of the art in the management and control of tuberculosis. E. Tuberculosis control programs should be evaluated periodically to ensure that program activities are cost effective. The closure of sanatoriums for hospitali- zation of patients who could be managed in the community in an ambulatory setting has proved cost effective, humane and clin- ically sound. Occasionally, hospitalization is appropriate to establish a diagnosis, im- plement therapy, or treat another condi- tion. Unnecessary hospitalization, or a pro- longed hospital stay, inflates the cost of tuberculosis care. These costs can be con- trolled by establishing admission and dis- charge criteria for hospitalization and length of stay. The value of clinic visits can be increased by using the time to verify regularity of drug ingestion and to check for drug toxic- ity. Short-course chemotherapy will eventu- ally decrease the clinic load. Directly admin- istered twice-weekly drug administration has proved to be the most cost-effective solution for the problem of noncompliant patients. Equipping a program to provide directly administered therapy may require a temporary increase in funding for addi- tional personnel and expanded record keep- ing systems. However, the elimination of unnecessary hospitalization and prevention of drug resistance or recrudescent disease will offset this expenditure. Nonproductive activities should be elimi- nated so that resources can be more effec- tively used. The routine screening of popu- lations with only slight risk of developing tuberculosis should be eliminated, e.g., per- sons working in restaurants or workers in the health delivery system who experience little or no patient contact should not have to be screened for tuberculosis. There is no longer any need for frequent chest radio- graphs to ascertain if chemotherapy is ef- fective in the management of disease, or for routine, periodic chest radiographs after treatment has been completed. The use of chest radiographs for screening or monitor- ing well populations prior to employment or simply to comply with outdated ordi- nances should be eliminated. Resources should be directed primarily to activities that help to ensure that patients take and complete chemotherapy and that contacts and high risk infected persons take and complete preventive therapy. This statement was prepared by an Ad Hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis and Pulmo- nary Infections. The Committee members were as follows: LAURENCE S. FarRER, M.D., Chairman JAMES P. FLYNN, M.D. RoBerT J. REzA, M.D. WILLIAM C. BalLey, M.D. RICHARD K. ALBERT, M.D. Bibliography This statement is one of a series of four state- ments on diagnosis, treatment and control of tuberculosis. For information on diagnostic methods refer to: Diagnostic Standards and Classification of Tuberculosis and Other Mycobacterial Dis- eases. Am Rev Respir Dis 1981; 123:343-58. The Tuberculin Skin Test. Am Rev Respir Dis 1981; 124:356-63. For information on treatment of tuberculosis and other mycobacterial diseases, refer to: Treatment of Tuberculosis and Other Myco- bacterial Diseases. Am Rev Respir Dis 1983; 127:790-6. General 1. Glassroth J, Robbins AG, Snider DE, Jr. Tuberculosis in the 1980’s. N Engl J Med 1980; 302:1441-50. 2. Comstock GW. Frost revisited: the modern epidemiology of tuberculosis. Am J Epidemiol 1975; 101:363-82. 3. Riley RL. Airborne infection. Am J Med 1974; 57:466-75. Surveillance 4. Barrett-Connor E. Periodic chest roentgeno- 43 AMERICAN THORACIC SOCIETY gram for the control of tuberculosis in health care personnel. Am Rev Respir Dis 1980; 122: 153-5. 5. Stead WW. Undetected tuberculosis in pris- on: source of infection for communities at large. JAMA 1978; 240:2544-7. 6. Stead WW. Tuberculosis among elderly per- sons: an outbreak in a nursing home. Ann Intern Med 1981; 94:606-10. Containment 7. Dandoy S. Current status of general hospital use for patients with tuberculosis in the United States. Am Rev Respir Dis 1982; 126:270-3. 8. Andrews RH, Devadatta S, Fox W, er al. Prevalence of tuberculosis among close family contacts of tuberculosis patients in South India and influence of segregation of the patient on the early attack rate. Bull WHO 1960; 23:463-510. 9. Kamat SR, Dawson JJY, Davadatta S. A controlled study of the influence of segregation of tuberculosis patients for one year on the attack rate of tuberculosis in a 5-year period in close family contacts in South India. Bull WHO 1966; 34:517-32. 10. Gunnels JJ, Bates JH, Swindoll H. Infectiv- ity of sputum-positive tuberculosis patients on chemotherapy. Am Rev Respir Dis 1974; 109: 323-30. 11. Johnston RF, Wildrick KH. The impact of chemotherapy on the care of patients with tuber- culosis. Am Rev Respir Dis 1974; 109:636-64. 12. Rouillon A, Pedrizet S, Parrot R. Trans- mission of tubercle bacilli: the effects of chemo- therapy. Tubercle 1976; 57:275-99. 13. Ferebee SH, Mount FW. Tuberculosis mor- bidity in a controlled trial of the prophylactic use of isoniazid among household contacts. Am Rev Respir Dis 1962; 85:490-521. 14. Komaroff AL. The practitioner and the compliant patient. Am J Public Health 1976; 66:833-5. 15. Maiman LA, Becker MH. The clinician’s role in patient compliance. Trends in pharmaco- logical sciences. December 1980, pp. 457-9. 16. O’Hanrahan M, O’Malley K. Compliance with drug treatment. Br Med J 1981; 283:298- 300. 17. McDonald RJ, Memon AM, Reichman LB. Successful supervised ambulatory management of tuberculosis treatment failures. Ann Intern Med 1982; 96:297-302. '' ''American Thoracic Society APPENDIX E MEDICAL SECTION OF THE AMERICAN LUNG ASSOCIATION TREATMENT OF TUBERCULOSIS AND OTHER MYCOBACTERIAL DISEASES THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY WAS ADOPTED BY THE ATS BOARD OF DIRECTORS, NOVEM- BER, 1982. THIS IS A JOINT STATEMENT OF THE AMERICAN THORACIC SOCIETY AND THE CENTERS FOR DISEASE CONTROL. Introduction Modern chemotherapy of tuberculosis is based on two bacteriological considera- tions. The first is selection of drug resistant mutants. The probability of the spontane- ous development of mutants resistant to an- tituberculous drugs occurs at the rate of about | x 10°¢. The probability that a single mycobacterium not previously exposed to antituberculous drugs is resistant to both of two drugs is assumed to be equal to the product of the probabilities of resistance to each drug alone (1x10°x1x10°¢=1x 10°'2), and is therefore negligible. The larg- est population of organisms in a human in- fection is in active cavities and rarely ex- ceeds 1x10°. Therefore, two drugs are almost always adequate to successfully avoid the selection of genetic mutants. The second consideration is the persis- tence of viable mycobacteria due to their slow or intermittent growth. This problem was previously overcome by extending treatment for eighteen months. Rifampin, taken in combination with isoniazid (INH) for nine months, is almost always successful if drug resistance is not a problem. It is postulated that there are three treat- able populations of tuberculosis organisms in the active human infection. The largest number are actively growing and are lo- cated extracellularly. These are the organ- isms that may become resistant, and there- fore are most effectively treated with two bactericidal drugs. A much smaller popula- tion of slowly or intermittently growing or- ganisms resides within macrophages at an acid pH. A third population consists of slowly or intermittently growing organisms in solid caseous areas where the pH is neu- tral. Rifampin is the only drug that is bacte- ricidal in all three of these populations. Isoniazid is bactericidal for both the active- ly growing organisms in cavities and for those within macrophages. Streptomycin and the other comparable injectible poly- peptides are bactericidal only for those ex- tracellular organisms growing actively. PZA is bactericidal only for intracellular veoReprinted by permission of the American Thoracic Society organisms. All other drugs are bacterio- static. The principles of therapy are derived from studies of adults with pulmonary tu- berculosis. Available evidence indicates that they should be generally applicable to chil- dren and persons with extrapulmonary tu- berculosis. Because of the high mortality from miliary and meningeal tuberculosis, as well as the potential risk of acute and chronic pericardial disease, the use of three drugs seems reasonable in these situations. Further details regarding these drugs are shown in table 1. Dosage is expressed in mg/kg for easier application to the pediat- ric patient. Treatment regimens for children are essentially the same as for adults with modification of dosages. Treatment Regimens Several regimens have been shown in con- trolled clinical trials to be highly effective in the treatment of tuberculosis. Drugs must be given in combination to avoid the emer- gence of resistant organisms. While the regimens discussed here have been shown to be effective in uncomplicated cases of pul- monary tuberculosis with drug susceptible organisms, other regimens may be more ap- propriate under certain conditions. (see subsequent section on Special Situations). Standard Treatment The simplest regimen is based on the ad- ministration of isoniazid and rifampin for nine months. In most reported studies, ethambutol or streptomycin has been added for an initial two to eight weeks. Good re- sults have also been reported using twice weekly administration of the isoniazid and rifampin after an initial one month of daily treatment. With these regimens, relapse rates of less than 3% have been reported. Recommended doses for the drugs are shown in table 1. In those few patients whose sputum is still culture-positive after three months of treatment with rifampin and INH, the duration of total treatment 45 should be extended at least six months be- yond the time of conversion. Isoniazid and rifampin for nine months is generally con- sidered the present treatment of choice. In patients with drug sensitive organisms it has been shown that treatment for less than nine months with isoniazid and rifam- pin is followed by a higher relapse rate. If isoniazid or rifampin cannot be used because of drug resistance or intolerance, the duration of treatment must be increased. Regimens shown to be effective when ri- fampin cannot be used are (/) isoniazid and ethambutol for a total of eighteen months, with the addition of streptomycin for an initial period of 1 to 2 months where the ini- tial bacterial population is believed to be high; and (2) isoniazid and streptomycin for a total of eighteen months. These regimens have been shown to be ef- fective when given on either daily or twice weekly basis in appropriate doses. Twice weekly treatment is appropriate in patients requiring directly supervised drug adminis- tration. If isoniazid cannot be used, rifampin and ethambutol can be given for a total of eigh- teen months. If neither isoniazid nor rifampin can be used, the patient must be given at least two and preferably three drugs to which his or- ganisms are known to be susceptible. These drugs must be given for at least eighteen months. Known or Suspected Drug Resistant Tuberculosis The following circumstances are associ- ated with a higher rate of drug resistant or- ganisms and require susceptibility studies: 1. tuberculosis among those known to have a higher prevalence of drug resistance, such as Asians or Hispanics, 2. previous treatment, 3. persistence of culture-positive sputum after 3 months of therapy, and Reprints may be requested from your state or local Lung Association. ''OV TABLE 1 TREATMENT OF MYCOBACTERIAL DISEASE IN ADULTS AND CHILDREN Commonly Used Agents Most Common Side Effects* Tests for Side Effects* Drug Interactionst Remarks’ Isoniazid Rifampin Streptomycin Pyrazinamide Ethambutol Dosage* Twice Weekly Daily Dose Dosage 5 to 10 mg/kg up 15 mg/kg PO to 300 mg PO or IM or IM 10 mg/kg up to 10 mg/kg up to 600 mg PO 600 mg PO 15 to 20 mg/kg up = 25 to 30 mg/kg to1gIM 15 to 30 mg/kg up = 50 to 70 mg/kg to2g PO 15 to 25 mg/kg 50 mg/kg PO Peripheral neuritis, hepatitis, hyper- sensitivity. Hepatitis, febrile reaction, purpura (rare). 8th nerve damage, nephrotoxicity. Hyperuricemia, hepatotoxicity. Optic neuritis (reversible with discontinuation of drug; very rare at 15 mg/kg), skin rash. SGOT/SGPT (not as a routine). SGOT/SGPT (not as a routine). Vestibular function, audiograms;t BUN and creatinine. Uric acid, SGOT/SGPT. Red-green color dis- crimination and visual acuity.t Diffi- cult to test ina child under 3 years. Phenytoin — synergistic Antabuse Rifampin inhibits the effect of oral contraceptives, quinidine, corti- costeroids, Coumarin drugs and methadone, digoxin, oral hypoglye- mics; PAS may interfere with absorption of rifampin. Neuromuscular blocking agents — may be potentiated to cause pro- longed paralysis. Bactericidal to both extracellular and intracellular organisms. Pyridoxine 10 mg as prophylaxis for neuritis; 50 to 100 mg as treatment. Bactericidal to all populations of organisms. Orange urine and other body secretions. Discolor- ing of contact lens. Bactericidal to extracellular organisms. Use with caution in older patients or those with renal disease. Bactericidal to intracellular organisms. Combina- tion with an aminoglycoside is bactericidal. Bacteriostatic to both intracellular and extracellu- lar organisms, primarily used to inhibit develop- ment of resistant mutants. Use with caution with renal disease or when eye testing is not feasible. Less Commonly Used Agents Capreomycin Kanamycin Ethionamide Para-aminosalicylic acid (aminosalicylic acid) Cycloserine 15 to 30 mg/kg up to1giM 15 to 30 mg/kg up to1giM 15 to 30 mg/kg up to1g PO 150 mg/kg up to 12 g PO 10 to 20 mg/kg up to1gPO 8th nerve damage, nephrotoxicity. Auditory toxicity nephrotoxicity, vestibular toxicity (rare). GI disturbance, hepatotoxicity, hypersensitivity. Gl disturbance, hypersensitivity, hepatotoxicity, sodium load. Psychosis, per- sonality changes, convulsions, rash. Vestibular function, audiograms;+ BUN and creatinine. Vestibular function, audiograms; BUN and creatinine. SGOT/SGPT SGOT/SGPT Psychologic testing. Neuromuscular blocking agents — may be potentiated to cause pro- longed paralysis. Neuromuscular blocking agents — may be potentiated to cause pro- longed paralysis. Alcohol — may aggravate or pre- cipitate psychiatric problems. Bactericidal to extracellular organisms in cavities. Use with caution in older patients. Rarely used with renal disease. Bactericidal to extracellular organisms. Use with caution in older patients. Rarely used with renal disease. Bacteriostatic to both intracellular and extracellu- lar organisms. Divided dose may help GI side effects; has a metallic taste. Avoid use during pregnancy. Bacteriostatic to extracellular organisms only. Gl side effects very frequent making cooperation difficult. Bacteriostatic to both intracellular and extracellu- lar organisms. Alcohol may aggravate psychiatric problems. Very difficult drug to use. Side effects may be blocked by pyridoxine, ataractic agents, or anticonvulsant drugs. * Check product labeling for detailed information on dose, contraindications, drug interaction, adverse reactions, and monitoring. t Reference should be made to current literature, particularly on rifampin, because it induces hepatic microenzymes and therefore interacts with many drugs. ¥ Initial examination should be done at start of treatment. ALBIDSOS DIOVHOHL NVOINSWY b6Z ''792 4. exposure to drug resistant tuberculosis. Ideally, susceptibility testing should be done on the initial specimens from patients in these groups. Selection of regimens should be based on drug susceptibility studies, or, when not available, on proba- bility data from susceptibility rates in the country or community of origin. General principles for therapy require that the regi- men contain two bactericidal drugs, when possible. Special Situations In a number of special situations the recom- mendations for treatment regimen require alteration. These include infection with my- cobacteria other than M. tuberculosis (see subsequent section on Preventive Therapy of Tuberculous Infection), tuberculosis in children, disease in organ systems other than the lungs, and the presence of certain patient characteristics, concurrent diseases, or the development of adverse drug reac- tions. Tuberculosis in Children Whenever there is an adult with infectious tuberculosis, all children who are house- hold contacts should receive isoniazid, 10 to 15 mg/kg of body weight per day (maxi- mum dose, 300 mg), for one year if infected without disease or for at least three months after the contact has been broken if their skin test remains nonsignificant. Approxi- mately 5% of those converting their skin tests will develop clinical disease within the first year following infection if they are not treated. Isoniazid therapy will usually pre- vent the development of such serious forms of the disease as tuberculous meningitis, miliary tuberculosis, and Pott’s Disease. More details on preventive therapy in chil- dren as well as adults are in the section on Preventive Therapy of Tuberculous Infection. Treatment of the Newborn. Management of infants known to be exposed to tubercu- losis varies with the severity of the disease and the efficacy of the treatment admin- istered to the source case. The newborn should receive a chest radiograph and a tu- berculin skin test (PPD S5TU). If neither suggests tuberculous disease, the infant should receive INH prophylaxis and be re- tested in three months, and if still nonsig- nificant, again in six months. Three months should allow sufficient time for the infec- tion to become established but cell-medi- ated immunity may not be fully developed until the child is six months of age. If the chest radiograph supports the diagnosis of tuberculosis, the patient should be treated with INH and rifampin for nine months and isolated from the source case until the patient (source) is judged noninfectious. If the follow-up skin test is significant, INH should be continued for one year. If skin tests are not significant INH should be stopped. If the source case is noncompliant, both the case and the infant should be placed on a supervised treatment program. When for some reason supervision is impos- sible, BCG may be considered for the new- born. Pulmonary Tuberculosis (Parenchymal). Although studies on children are not yet available, an approach similar to that used for adults appears logical. For drug suscep- tible tuberculosis, a short course treatment regimen (9 months) with isoniazid and ri- fampin is recommended. Dosages on a mg/kg basis are available in table 1. Other regimens include isoniazid and ethambutol for 18 months. When drug resistance is a problem, other regimens based on the previously stated principles of therapy are Acceptable. All regimens must contain at least two drugs to which the organisms are susceptible. Mediastinal Lymphadenopathy. When no lung lesion can be seen, INH may be given alone for one year. If exposure has been ex- tensive, host immunity is questioned, or a focal lesion is present, a two-drug regimen should be used. If the regimen is INH and rifampin, nine months of therapy is suffi- cient. Endobronchial Tuberculosis. Occasionally, endobronchial disease may result from pen- etration of the bronchus by caseous lymph nodes resulting in caseous material or poly- poid formation within the bronchus. Bron- choscopy is desirable in such cases, but should be carried out only if an experi- enced bronchoscopist and an anesthesiolo- gist are available, and the hospital is suit- ably equipped to study infants. In addition to antimicrobial therapy, prednisone 1 mg/ kg of body weight for six to twelve weeks early in the course of disease has been thought by some to reduce endobronchial scar formation. Extrapulmonary Tuberculosis. Extrapul- monary tuberculosis forms an increasing proportion of newly reported cases in the United States. The small number of cases involved precludes controlled clinical trials designed to define the best chemotherapeu- tic regimens for the various categories of ex- trapulmonary disease. As a general rule, regimens that are adequate for the treat- ment of pulmonary tuberculosis in adults and children will also be effective in extra- pulmonary disease. The bacterial popula- tion is usually considerably smaller in the latter. Tuberculous Meningitis. Whereas INH, ri- fampin, and PZA all cross the blood-brain barrier without difficulty, other antituber- culosis drugs may appear in lower con- centrations in the central nervous system. During acute meningeal irritation, all drugs diffuse well, thus streptomycin may be a useful drug in treating TB meningitis. Three drugs are often used, particularly in the ear- 47 AMERICAN THORACIC SOCIETY ly part of treatment, although there are no data to show that three drugs are more ef- fective than two. Delay in treatment may result in serious central nervous system con- sequences. The use of adrenocorticosteroids to pre- vent the development of internal hydro- cephalus is strongly recommended by some pediatricians. Disseminated Tuberculosis (including Mil- iary). Although studies have shown that INH and rifampin provide effective therapy for disseminated tuberculosis, an_ initial three-drug regimen is frequently used in the treatment of such serious disease. Adrenocorticosteroids are sometimes given to severely ill patients. These drugs may reduce symptoms but have not been proven to affect outcome. Tuberculous Lymphadenitis. Treatment for this condition is the same as for pulmonary tuberculosis. Excisional biopsy of the lesion should be done for diagnosis. Even if com- plete excision is performed, chemotherapy is indicated. Tuberculosis of the Bones and Joints. Treatment is the same as for pulmonary tu- berculosis with the exception that all super- ficial and accessible abscesses should be drained. Immobilization of the joint is not necessary unless neurological symptoms in- dicate spinal column instability. Genitourinary Tuberculosis. Treatment is the same as it is for pulmonary tuberculosis. Because ureteral stricture may appear dur- ing therapy and for several years following therapy, periodic intravenous pyelogram or ureteral calibration is recommended. Gastrointestinal Tuberculosis. Treatment is the same as that for pulmonary tubercu- losis. Pericardial Tuberculosis. The chemother- apy is the same as for pulmonary tuberculo- sis, but because constrictive pericarditis re- sults in some cases despite proper therapy, pericardectomy will at times be necessary. Adrenocorticosteroids during the first few months of chemotherapy may decrease the risk of constrictive pericarditis and subse- quent need for surgery. Pleural Tuberculosis. Pleural tuberculosis is the most common form of extrapulmonary tuberculosis and responds well to standard chemotherapy. A thoracentesis and pleural biopsy should be performed for diagnosis and it is helpful to remove most of the fluid when these procedures are completed in order to decrease the rare complication of pleural scar formation. Before the days of chemotherapy, tuberculosis pleural effu- sion was frequently complicated by a bron- chopleural fistula at times requiring a vari- ety of surgical drainage procedures. These ''AMERICAN THORACIC SOCIETY complications have fortunately become rare. Other Conditions Affecting Therapy Tuberculosis during Pregnancy. Tuberculo- sis should be treated without delay when discovered during pregnancy. Ethionamide, streptomycin, and other injectable antitu- berculosis drugs may be toxic to the fetus and should generally be avoided. INH and rifampin cross the placental barrier but have not been associated with tetratogenic effects. No other antituberculous drugs have been shown to have an adverse effect on the fetus. Where feasible, tuberculosis during pregnancy should be treated by at least two of the following three drugs: INH, rifampin, or ethambutol. Renal Disease. If possible, patients with renal failure should not be given any antitu- berculous medications that have nephro- toxic effects or that are cleared by the kid- neys. Drugs in these categories include streptomycin, kanamycin, capreomycin, ethambutol, and cycloserine. If drug resis- tance or toxicity requires the use of any from this list, blood levels must be obtained to permit appropriate changes in dose or in the interval between doses. Hepatic Disease. Mild hepatic dysfunction, as seen in alcoholism, does not necessarily influence the choice of drugs. However, monitoring liver function is important. Ele- vations in the serum GOT or GPT to three- five times normal should lead to a reassess- ment of the patient’s tuberculosis and alco- holism. Regimens may be continued, stopped, interrupted, or changed as a result of this assessment. Patients with hepatic failure associated with encephalopathy or hepatocellular damage with a persistent SGOT elevation of greater than 6 to 8 times baseline should be treated with drugs that are excreted by the kidneys rather than metabolized in the liver. Should rifampin, isoniazid, PZA, ethionamide, and PAS be excluded because they are potentially hépatotoxic, no other effective agents remain. Streptomycin and ethambutol are safe, but a third drug may be required. Isoniazid or rifampin may be tried cautiously but should be stopped im- mediately if liver function deteriorates. Malabsorptive States. The absorption of oral medication appears to be normal in patients having upper or lower bowel resec- tion provided the jejunum is retained. When the jejunum is resected, rifampin and ethambutol absorption is reduced. Treatment of Patients who cannot take Oral Medications. When treating patients who cannot swallow, administration of drugs via a gastrostomy tube is suggested. Patients who require total parenteral ther- apy can be treated with streptomycin, INH, rifampin, and other injectable polypep- tides, such as kanamycin or capreomycin. Surgery. Surgery is rarely indicated in the treatment of tuberculosis. It may be con- sidered as ancillary therapy in treating cer- tain cases of drug-resistant disease. Drug Interactions. Certain drug interac- tions are extremely important. See table 1 for specific interactions. The current litera- ture should be reviewed when prescribing antituberculous medications to patients taking any other drug. A record should be made of all the drugs a patient is receiving. Use of Pyridoxine. Pyridoxine is recom- mended for those patients taking isoniazid who have evidence of nutritional deficier- cy. Likely candidates include alcoholics, the aged, pregnant women, and those with neu- rologic problems. Because patients with uremia or diabetes are prone to peripheral neuropathies, the addition of pyridoxine is suggested to minimize diagnostic confusion. Preventive Therapy of Tuberculous Infection Introduction A substantial body of scientific data testi- fies to the value of isoniazid in prevention of tuberculosis. The extensive trials con- ducted by the U.S. Public Health Service show a sizable and consistent reduction of morbidity in groups treated with INH. Pre- ventive therapy presumably acts by dimin- ishing the bacterial population in “healed” or radiographically invisible lesions. Data have now been accumulated that indicate the beneficial effect of INH in those with a significant tuberculin skin test (see Diag- nostic Standards and Tuberculin Skin Test and Classification of Tuberculosis and Other Mycobacterial Diseases) persists for up to 20 years and presumably for life. It is, in reality, treatment of tuberculous infection. Less commonly, medication is given to per- sons who are exposed to tuberculosis but not yet infected, in an attempt to prevent the establishment of a tuberculous infec- tion. In this situation, prophylaxis is protec- tive only while the individual is taking medi- cation. Although INH is usually a safe drug, like all medicines it is occasionally associated with adverse reactions. The most significant of these is hepatitis. The occurrence of hep- atitis among isoniazid-treated individuals has been extensively studied. It is clear that elevation of serum aminotransferase (trans- aminase) activity, probably reflecting mild hepatic dysfunction, occurs in 10 to 20 per- cent of persons taking INH. This type of aonormality usually occurs within the first 6 months of treatment but can occur at any time during therapy. Usually enzyme levels return to normal despite continuation of medication. Only occasionally does progressive liver damage and clinical hepatitis occur. Although the mechanism underlying INH associated hep- atitis is unclear, it is now established that the frequency of progressive liver damage 48 793 generally increases with age. Thus, it is rare in persons under age 20. The observed fre- quency in other age groups is as follows: Ages Frequency 20 to 34 =: Up to. 0.3% 35to49 Upto 1.2% 50 to 64 Upto 2.3% The hepatitis case rate does not appear to increase further beyond age 64 years. Drinking alcohol, especially on a daily ba- sis, may enhance the risk of INH-associated hepatitis. Persons for Whom Preventive Therapy is Recommended Every tuberculin skin test reactor is at some risk of developing tuberculosis and presumably can benefit from INH preven- tive therapy. Not all reactors are at equal risk, as certain host factors increase the probability. Priorities can be set for preven- tive therapy that take into consideration the risk of developing tuberculosis compared with the risk of INH toxicity. The recom- mendations outlined below for the use of INH with appropriate supervision are based on a comparison of the risk of hepatic in- jury during the period of treatment with the potential lifelong benefit of preventive ther- apy. The value of preventive therapy may be further enhanced in those clinical situa- tions where tuberculosis tends to present as either a particularly aggressive or occult dis- ease. Also of importance is the benefit to society derived from preventive therapy, because prevention of tuberculosis pre- cludes the spread of new infection. Isoniazid preventive therapy is recom- mended for the following persons listed in order of priority: 1. Household members and other close associates of potentially infectious tubercu- losis cases. Because many persons in this group will have been recently infected by the index case, their risk of developing tu- berculosis will be relatively high, approxi- mately 2 to 4 percent for the first year with individuals who have a significant tubercu- lin skin test having the greatest risk. The risk for very young children and adolescents may be as much as twice the adult risk. Fur- thermore, individuals who do not develop disease in the period immediately following infection appear to be at some risk of doing so for the remainder of their lives. All contacts with a Mantoux tuberculin skin test reading of 5 mm or more and with- out a history of reaction in the past, should be considered as recently infected with M. tuberculosis and receive preventive therapy. Some contacts with nonsignificant tuber- culin skin test reactions should be consid- ered for preventive therapy. At highest risk are children who are contacts of bacterio- logically positive patients and who may be infected but may not yet have converted their tuberculin skin test. Some clinicians ''794 prescribe preventive therapy for three months for children other than newborns. After three months, the children receive a repeat tuberculin skin test. If the reaction is significant, therapy should be continued for a total period of 12 months; if nonsignifi- cant, and exposure has ended, therapy may be discontinued. For adult contacts with nonsignificant tuberculin skin test reac- tions, factors such as the state of infectious- ness of the source case and the risk of drug side effects should be considered before prescribing preventive therapy. If therapy is not prescribed, the tuberculin skin test should be repeated in 3 months and preven- tive therapy prescribed at that time if skin test conversion has occurred and the chest roentgenogram remains negative. 2. Newly infected persons. The risk of developing tuberculous disease for the new- ly infected is concentrated during the first year after infection. Because this excess risk is concentrated in the first year or so, the term “newly infected persons” should be ap- plied to those who have had a tuberculin skin test conversion within the past two years. Reactors under 5 years of age are at great risk because they have been recently infected, certainly within five years and also because their immune system is less well developed. 3. Persons with significant reactions to tuberculin skin test and abnormal chest roentgenograms. Persons with past tuber- culous disease not previously treated by adequate chemotherapy and tuberculin skin test reactors with roentgenographic findings consistent with nonprogressive tuberculous disease (i.e., stable paren- chymal lesions and not. isolated calcifica- tions or pleural thickening) should receive preventive therapy. The rate of reactivation in such groups, if untreated, ranges from about 0.5 to 5 percent per year. Although the risk appears lowest for those persons whose roentgenograms have been stable longest and for those with the most limited degree of involvement, even for these per- sons the tuberculosis risk is still at least several times greater than for persons hav- ing normal chest roentgenograms. 4. Persons with significant reactions to tuberculin skin test and who are in special clinical situations. The special situations that may require preventive therapy when tuberculous infection is also present are: a) Silicosis b) Diabetes mellitus. The risk for this group may be as much as four times that of the general population. Particularly, but not exclusively, at risk are brittle juvenile onset diabetics. c) Prolonged therapy with adrenocorti- costeroids. Because steroids are pre- scribed for many conditions, some of which are likely to alter host defenses, it is not possible at present to determine the exact risk of tuberculosis associated with steroid therapy. Tuberculosis developing during steroid therapy is more likely to be disseminated or diagnosed late in its course. There is insufficient data at pres- ent to categorically recommend INH pre- ventive therapy for persons treated with low daily doses of steroids (e.g., 10 mg prednisone) for asthma or with chronic alternate day steroids. Because long-term steroid requirements are unpredictable and because the frequency of INH-asso- ciated hepatitis increases with age, it may be prudent to consider some of these per- sons for preventive therapy. d) Immunosuppressive therapy e) Some hematologic and reticuloendo- thelial diseases, such as leukemia or Hodgkin’s, J) Chronic hemodialysis. There have been a number of recent reports suggest- ing that persons on chronic hemodialysis are at increased risk of developing tuber- culosis. They appear particularly predis- posed to developing extrapulmonary and disseminated disease. Though some of these reported individuals had additional potentially predisposing conditions such as diabetes mellitus, the majority did not. Because many of these individuals will be anergic, a documented history of a prior significant tuberculin skin test is an indica- tion for preventive therapy if it has not been previously given. &) Clinical situations associated with substantial rapid weight loss or chronic undernutrition. These situations include: intestinal bypass surgery for obesity, which appears to carry an increased risk particularly for extrapulmonary tubercu- losis; the postgastrectomy state; chronic ulcer disease; chronic malabsorption syn- dromes; and carcinoma of the head and neck. The postgastrectomy state may in- crease the risk of developing tuberculosis without % ight loss. 5. Tuberculin skin test reactors under 35 years of age with none of the above risk Sactors. Screening Procedures Before INH preventive therapy is started for any of the above indications, it is impor- tant to: 1. Exclude bacteriologically positive or progressive tuberculous disease. Every per- son who has a significant reaction should have a chest radiograph taken. If there are findings consistent with pulmonary tuber- culous disease, further studies— medical evaluation, bacteriologic examinations, and comparison with previous radiographs— should be made to exclude progressive dis- ease. Appropriate evaluation should be per- formed if extrapulmonary tuberculosis is suspected. Persons with progressive disease require more intensive chemotherapy than is given for prevention. 2. Question for a history of prior INH administration to exclude those who have had an adequate course of the drug. 49 AMERICAN THORACIC SOCIETY 3. Check for contraindications to the ad- ministration of INH for preventive therapy. These include: a. previous INH-associated hepatic in- jury. b. history of severe adverse reactions to INH, such as drug fever, rash, and arthritis. c. acute liver disease of any etiology. 4. Identify patients for whom preventive therapy is not contraindicated but in whom special precautions are indicated. These include: a. Age greater than 35 years. b. Concurrent use of any other medica- tion on a long-term basis (in view of pos- sible drug interactions). See table 1. c. Daily use of alcohol, which may be as- sociated with a higher incidence of INH hepatitis. d. History of previous discontinuation of INH because of possible, but not defi- nitely, related side effects, e.g., head- aches, dizziness, nausea, etc. e. Possibility of current chronic liver disease. f. Existence of peripheral neuropathy or of a condition such as diabetes mellitus or alcoholism, which might predispose to the development of neuropathy. g. Pregnancy and breast feeding. Al- though no harmful effects of INH to the fetus have been observed, its use during pregnancy generally is for those with tu- berculous disease. Isoniazid preventive therapy generally should be delayed until after delivery. There does not appear to be any substantial increment in tubercu- losis in risk for women during pregnancy. An exception is with pregnant women likely to have been recently infected. Then, INH preventive therapy should be- gin when the infection is documented, but after the first trimester. Physicians who care for nursing mothers should be made aware that INH is secreted into breast milk, although there is no evidence of adverse effects of INH on nursing infants. Administration of Preventive Therapy A single drug, INH, is used for preventive therapy in a dose of 300 mg per day for adults and 10 to 15 mg per kg body weight per day, not to exceed 300 mg per day, for children. The medication is administered as a single caily dose for 12 months. There is some evidence to suggest that 6 months of INH preventive therapy may confer a sub- stantial degree of protection, but protection conferred by such shortened regimens may not be as long lasting as that derived from a full year of therapy. Durations of therapy longer than one year do not provide addi- tional benefit. There are no data on the ef- fectiveness of 9-month regimens. Monitoring Preventive Therapy Office, clinic or home visits, or telephone calls should be made at monthly intervals. ''AMERICAN THORACIC SOCIETY The individual receiving preventive therapy or a responsible adult in a household with children on preventive therapy should be questioned carefully at monthly intervals for the following: 1. Symptoms consistent with those of liver damage or other toxic effects; that is, unexplained anorexia, nausea, vomiting, fatigue or weakness of greater than 3 days duration; persistent paresthesias of the hands or feet; 2. Signs consistent with those of liver damage or other toxic effects; that is, per- sistent dark urine, icterus, rash, elevated temperature of greater than 3 days duration without explanation, abdominal tenderness (especially right upper quadrant); 3. Other signs and symptoms the patient may report. Individuals should be advised that if any of the above signs or symptoms occur during preventive therapy, they should report im- mediately to the clinic or primary care pro- vider for evaluation. The use of a standard- ized form for interviewing at each individual visit will help insure alertness to all signs and symptoms, expedite the interview pro- cess, and provide for standardized data collection. 4. Laboratory Tests As noted, 10 to 20 percent of individuals receiving INH will develop some mild ab- normality of liver function tests. These ab- normalities tend to resolve even if INH is continued. It is not recommended that liver function tests (e.g., serum glutamic oxalo- acetic transaminase (SGOT), serum gluta- mic pyruvic transaminase (SGPT), serum bilirubin, alkaline phosphatase) be routine- ly performed to monitor preventive therapy for individuals under 35 years of age. In evaluating signs and symptoms of adverse reactions, such tests are mandatory. Be- cause there is higher frequency of INH- associated hepatitis among persons over 35 years of age, they should have a trans- aminase test at the start of, and periodical- ly during, the course of therapy. If any of these tests exceed three to five times the laboratory normal, the decision to continue the INH should be reconsidered. Labora- tory tests of this type are not a substitute for a clinical evaluation at monthly inter- vals, nor for the prompt assessment of signs or symptoms of adverse reactions occurring between regularly scheduled evaluations. Alternative Forms of Tuberculosis Prevention Although other drugs might also be ef- fective for preventive therapy, there are currently no data available documenting the efficacy of any drug other than INH. Nonetheless, there are occasional situations in which alternative forms of preventive therapy might be desirable. Management of close contacts of INH- resistant cases. At least 3 alternatives exist in the situation where there is confidence that contact is to a known INH-resistant case: (/) prescribe INH in the hope that it will still be effective in vivo, (2) prescribe another drug (or drugs) under the assump- tion that’it (they) would be effective, (3) ob- serve the individual and prescribe no pre- ventive therapy. At the present time it ap- pears reasonable to treat child contacts and those adult contacts who appear particular- ly susceptible to tuberculosis (e.g., immune compromised hosts) with rifampin. Some clinicians would add a second drug, such as ethambutol, to which the organism is be- lieved sensitive. Preventive therapy is given in standard therapeutic doses and therapy should be continued for 12 months. Other contacts would be treated in a similar fash- ion and given the usual INH preventive therapy or would be observed. In situations in which there is less confidence that the in- fection is due to an INH-resistant case, INH should be used for preventive therapy. Management of persons intolerant to INH. An approach similar to that taken for contacts of INH-resistant cases can be used here with the exception, of course, that INH is not an alternative. BCG. The bacillus of Calmette and Guerin (BCG) was derived from a strain of Mycobacterium bovis attenuated through years of serial passage in culture at the Pas- teur Institute, Lille, France. There are many BCG vaccines available, most of which have not been recently studied. The protection obtained from studies of previ- ous vaccines has varied from 0 to 80 per- cent. The most recent large trial, conducted in South India, failed to show a protective effect despite the fact that the vaccines used were believed to be two of the most potent available. Even if vaccines of proved efficacy and safety were available, then potential benefit of BCG vaccination in a nation such as the United States would be small because most tuberculous disease occurs in persons who have already been infected. Such persons will not benefit from BCG. This risk of be- coming infected in the United States is very low. The BCG has been associated with a vari- ety of infrequently occurring adverse reac- tions including osteomyelitis, disseminated BCG infection, and death. The frequency of these reactions probably varies with the vaccine used, the intensity with which ad- verse reactions are sought, and the popula- tion vaccinated. The BCG vaccination may cause tuberculin skin test conversion, thus rendering that test less useful. Because of these potential shortcomings, BCG is recommended only as an alternative approach when INH preventive therapy cannot be used. In such situations BCG vaccination should be considered for those persons who have no reaction to the tuber- culin skin test and who have repeated expo- sure to potentially infectious (e.g., sputum- positive) tuberculosis. Depressed host im- munity or pregnancy should be considered 50 795 contraindications to BCG administrations. If a newborn is to be vaccinated, one half the usual dose should be used. Treatment of Disease Caused by ‘Mycobacteria Other Than M. tuberculosis Several species of mycobacteria cause tu- berculosis in man. It must be kept in mind, however, that these species and other myco- bacteria are normal inhabitants of the envi- ronment and therefore are more frequently observed in man as nondisease and existing as saprophytes or colonizers. Establishing a firm diagnosis is essential before treatment is initiated. A single or intermittent isolate of one of these organisms is common and often is not associated with disease. In gen- eral, the diagnosis of a disease that requires treatment is based on culturing multiple colonies on several occasions from patients with a progressive disease complex that resembles tuberculosis. M. kansasii, the M. avium-intracellulare complex, and the M. fortuitum complex are the species most frequently encountered as pathogens. Anti- mycobacterial drug susceptibility studies as currently done are of limited value for choosing treatment regimens because resis- tance to several of the drugs is common, and the correlation of the in vitro and in vivo results is poor. Disease caused by M. kansasii responds well to chemotherapy. Initial treatment regimens should always contain rifampin. An additional drug or two is also necessary for success. Isoniazid and ethambutol or streptomycin are generally recommended. Treatment is continued for 18 to 24 months although shorter term regimens are current- ly being evaluated. Organisms of the M. avium-intracellulare complex are resistant to the majority of the antituberculosis drugs. There may be in vitro susceptibility to ethionamide, cyclose- rine, rifampin, or to other drugs on occasion. Multiple drug regimens may be effective against the disease, and some investigators suggest that the best results are obtained with 4 or more drugs. Surgical resection has been advocated for localized disease. Con- comitant use of multiple drugs before and following surgery is recommended. If the disease is not progressive and drugs cause problems, they may be discontinued. Disease with the M. fortuitum complex (M. fortuitum, M: chelonei) is found most commonly in an extrapulmonary site and is frequently associated with apparent injury to soft tissue. The organisms are resistant to the antituberculosis drugs. Drainage, de- bridement, or excision are the treatments of choice. Where chemotherapy is necessary, multiple antituberculosis drugs can be tried; but response is unpredictable. Other antibi- Otics such as Amikacin and Doxycycline and Sulfonamides are reported to be effec- tive in some cases. M. bovis and disseminated infection ''79€ caused by BCG are rarely distinguished from M. tuberculosis in the laboratory. These should be treated in a similar man- ner. It should be noted that patients may be infected with both M. tuberculosis and other mycobacteria simultaneously. This statement was prepared by an Ad Hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis and Pulmonary Infections and the Scientific Assembly on Pediatrics. Members of the Committee were: WiLiiaM C. BatLey, M.D., Chairman RICHARD K. ALBERT, M.D. Paut T. Davipson, M.D. LAURENCE S. FarerR, M.D. JEFFREY GLASSROTH, M.D. Epwin KENpIG, Jr., M.D. RoBert G. Loupon, M.B.B., Cu. Laura S. INSELMAN, M.D. Bibliography This statement is one of a series of four state- ments on diagnosis, treatment and control of tuberculosis. For information on diagnostic methods refer to: Diagnostic Standards and Classification of Tuberculosis and Other Mycobacterial Dis- eases. Am Rev Respir Dis, 1981; 123:343-51. The Tuberculin Skin Test. Am Rev Respir Dis 1981; 124:356-63. For information on screening for tuberculosis, management of contacts, and organization of control programs refer to: Control of Tuberculosis. Am Rev Respir Dis, 1983; (submitted for publication). General Overview 1. Green GMG, Daniel TM, Ball WCB, eds, Koch Centennial Supplement. Am Rev Respir Dis, 1982; 125:1-132. A collection of papers on the scientific discov- eries in immunology, microbiology, epidemi- ology, and chemotherapy from 1882 to 1982, which have led to the development of modern tuberculosis treatment and control programs. 2. Glassroth J, Robbins AG, Snider DE. Tu- berculosis in the 1980’s. N Engl J Med, 1980; 302:1441-50. This paper presents a review of research in the prevention and treatment of tuberculosis. It presents the basic principles for the medical management of tuberculosis and tuberculous infection. Epidemiology of Tuberculosis . 3. Comstock GW. Frost revisited. The modern epidemiology of tuberculosis. Am J Epidemiol- ogy 1975; 101:363-82. A comprehensive review of epidemiologic studies on the incidence of tuberculosis and tu- berculous infection, which provide the basis for modern control programs. 4. Horwitz O, Wilbek E, Erickson PA, Epidemi- ologic basis of tuberculosis eradication. Bull WHO 1969; 41:95-113. A careful analysis of the incidence and preva- lence of tuberculosis in developed countries through 1968 with projections for the eradica- tion of the disease. Prevention of Tuberculosis 5. Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis: a general review. Adv Tu- berc Res 1970; 17:28-106. A comprehensive review of the clinical trials of preventive therapy for tuberculous infection. This paper documents the effectiveness of che- moprophylaxis. 6. WHO. Vaccination Against Tuberculosis. WHO/Technical Report Series, 652, 1980. This monograph presents the results of BCG trials conducted throughout the world. The paper presents the limitations of BCG as a pre- ventive measure. 7. Kopanoff DE, Snider DE, Caras GJ. Isonia- zid-Related Hepatitis: A U.S. Public Health Ser- vice Cooperative Surveillance Study. Am Rev Respir Dis 1978; 117:991-1001. This article reports the results of an isoniazid surveillance study conducted by the Centers AMERICAN THORACIC SOCIETY for Disease Control. This information pro- vides a basis for weighing the benefits of isoni- azid in preventing tuberculosis against the risk of its causing death. Treatment of Tuberculosis 8. Johnston RF, Wildrick KH. State of the Art: The impact of chemotherapy for pulmonary tu- berculosis. Am Rev Respir Dis 1974; 109:636-64. A review of the nature and scope of the tuber- culosis problem is presented. This paper re- views the clinical therapy trials up to 1974 that demonstrate the efficacy of chemotherapy, and based on this, presents recommendations for treatment. 9. Fox W. The chemotherapy of pulmonary tu- berculosis: a review. Chest 1979; 76:785-96. This article presents a review of data derived from the initial clinical trials of short-course treatment regimens. These studies provide the basis for the current recommendations for tu- berculosis chemotherapy. 10. Kopanoff DE. A continuing survey of tuber- culosis primary drug resistance in the United States: March 1975 to November 1977. Am Rev Respir Dis 1978; 118:835-42. This is a report of a survey conducted from 1975 through 1977 of the tuberculosis primary drug resistance. This study identified those population groups with high resistance rates to the major antituberculosis drugs. 11. Snider DE, Rogowski JR, Zierski M, Bek E, Long M. Successful intermittent treatment of smear-positive pulmonary tuberculosis in six months: a cooperative study in Poland. Am Rev Respir Dis 1982; 125:265-7. The report of a study of six months of therapy for tuberculosis, which demonstrates the effec- tiveness of supervised intermittent therapy regimens. Nontuberculous Mycobacteria 12. Wolinsky E. State of the Art: Non-tubercu- lous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119-27. A comprehensive review of the bacteriology of non-tuberculous mycobacteria and discussion of clinical manifestation of diseases caused by these organisms. #U.S, GOVERNMENT PRINTING OFFICE: 1983-417-303 51 '' ''FDA 81-8178 FDA 81-8179 FDA 82-8034 FDA 82-8042 FDA 82-8054 FDA 82-8056 FDA 82-8070 FDA 82-8127 FDA 82-8152 FDA 82-8180 FDA 82-8181 FDA 82-8182 FDA 82-8183 FDA 82-8184 FDA 82-8185 FDA 82-8186 FDA 82-8187 FDA 82-8189 FDA 82-8190 FDA 82-8191 FDA 82-8192 FDA 82-8193 FDA 82-8194 FDA 82-8195 FDA 82-8196 FDA 82-8197 FDA 82-8198 FDA 83-8027 FDA 83-8152 FDA 83-8154 FDA 83-8202 Procedures to Minimize Diagnostic X-Ray Exposure of the Human Embryo and Fetus (PB 82-110552, $8.50). A Microprocessor-Based True-RMS Line Voltage Monitor (GPO 017-015-00202-1, $3.25) (PB 82-125022, mf only). Report of State and Local Radiological Health Programs (PB 82-250028, $8.50). CSU-FDA Collaborative Radiological Health Laboratory Annual Report 1980 - Health Effects of Prenatal and Postnatal Whole-Body Exposure to Ionizing Radiation in the Beagle Dog (PB 82-177817, $14.50). 13th Annual National Conference on Radiation Control - Problems, Trends, and Issues: The Need for Redefinition (PB 82-237298, $23.50). Nationwide Evaluation of X-Ray Trends: Medical X-Ray Data (brochure) (supersedes FDA 78-8056, May 1978). Bureau of Radiological Health Publications Subject Index (supersedes FDA 81- 8070, November 1980) (PB 82-160250, $7.00). Guide for the Filing of Annual Reports (21 CFR Subchapter J, Section 1002.11) (PB 82-214206, $10.00). Annual Report of the Division of Biological Effects, Bureau of Radiological sso Fiscal Year 1980 (October 1, 1979 - September 30, 1980) (PB 82-215500, 11.50). Radiation Safety in Nuclear Medicine: A Practical Guide (PB 82-159963, $14.50). A Primer on Theory and Operation of Linear Accelerators in Radiation Therapy (GPO 017-015-00204-7, $4.25) (PB 82-162306, mf only). Sourcebook of Educational Materials for Dental Radiology (PB 82-165580, $10.00). Report of Classroom Use of Sodium Vapor Lamps (PB 82-169517, $7.00). A Guide for the Submission of Initial Reports on Diagnostic X-Ray Systems and Their Major Components (Revised January 1982) (PB 82-185158, $11.50). Performance Evaluation of RF Electric and Magnetic Field Measuring Instruments (PB 82-195009, $8.50). High-Yield Criteria for Panoramic Radiography (GPO 017-01 5-00207-1, $4.75) (PB 82-229543, mf only). MTF's and Wiener Spectra of Radiographic Screen-Film Systems (GPO 017-015- 00205-5, $5.50) (PB 82-215120, mf only). A Sensitometric Evaluation of Film-Chemistry-Processor Systems in the State of New Jersey (PB 82-263310, $7.00). An Overview of Ultrasound: Theory, Measurement, Medical Applications, and Biological Effects (GPO 017-015-00206-3, $6.00) (PB 83-111583, mf only). Workshop Manual for Radionuclide Handling and Radiopharmaceutical Quality Assurance (PB 83-105569, $10.00). Concepts and Approaches for Minimizing Excessive Exposure to Electromagnetic Radiation from RF Sealers (PB 83-111302, $8.50). United States Public Health Service Personnel Monitoring Program: Instruction Manual. The Utility of Administrative Diagnostic X Rays (PB 83-118497, $11.50). Guide for Compliance with Television Receiver Reporting and Testing Program Requirements (21 CFR 1002.10 and 1002.12) (PB 83-125773, $8.50). Background for Protective Action Recommendations: Accidental Radioactive Contamination of Food and Animal Feeds (PB 83-120246, $10.00). Technology Assessment Forum on Dental Radiology (PB 83-116418, $40.00). The Role of the U.S. Public Health Service in Radiological Health: 1946-1969 (PB 83-175695, $25.00). Directory of Personnel Responsible for Radiological Health Programs (supersedes FDA 82-8027, October 1981). Annual Report of the Division of Biological Effects, Bureau of Radiological Health (Fiscal Year 1981) (PB 83-165779, $11.50). Quality Control Procedures for Field Uniformity Correction Devices in Nuclear Medicine (GPO 017-015-00209-8, $2.75). A Microprocessor Controlled Instrument for Measurement and Display of X-Ray Waveforms (PB 83-215509, $10.00). 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