Trends and Occupational Associations in Incidence of Hospitalized Pulmonary Sarcoidosis and Other Lung Diseases in Navy Personnel*: A 27-Year Historical Prospective Study, 1975-2001
Study objectives: This study examines long-term trends in incidence rates of hospitalized pulmonary sarcoidosis in a large cohort of Navy personnel, and evaluates the possible relationship of sarcoidosis with occupation.
Design: Incidence rates of first hospitalizations were determined for black and white male Navy enlisted personnel on active duty from 1975 to 2001.
Setting: Navy service includes a potential for exposure to a variety of substances, including nonskid coatings used on ship decks that may be aerosolized during removal. Particulate matter containing aluminum, titanium, and silicates has been identified in nonskid samples. Specific occupational groups may have had greater exposure potential than others.
Patients or participants: Hospitalized cases included sarcoidosis (n = 674), asthma (n = 3,536), emphysema and chronic bronchitis (n = 1,103), respiratory conditions due to fumes and vapors (n = 61), and pneumoconiosis (n = 51) observed in 9,953,607 person-years of active- duty service.
Interventions: None. However, improvements were made in personal protective gear and other countermeasures to prevent or limit respiratory exposures during service.
Measurements and results: Annual overall hospitalized sarcoidosis incidence rates per 100,000 were 24.9 for black men and 3.5 for white men (black/white ratio of 7.1, p
Conclusions: There was a steep decline in incidence of hospitalized sarcoidosis in blacks in the Navy. Occupational associations suggest the possibility that a dust or moisture- related lung disease may have been erroneously classified as sarcoidosis, or, alternatively, that sarcoidosis had a previously unrecognized occupational component. (CHEST 2004; 126:1431-1438)
Key words: epidemiology; military populations; occupation; occurrence; sarcoidosis
Abbreviations: CL = confidence limit; ICD-9-CM = International Classification of Diseases, Ninth Edition, Clinical Modification; OR = odds ratio; SIR = standardized incidence ratio
Sarcoidosis is a multisystem, noncaseating, granulomatous disease of unknown etiology. Its symptoms are highly variable and may involve any organ, but > 90% of cases involve the lungs.1-4 Presenting signs of lung abnormalities found on chest radiography include mediastinal widening due to bilateral hilar lymphadenopathy, and diffuse pulmonary infiltrative and nodular changes.5 Common respiratory symptoms such as cough and shortness of breath may accompany the initial presentation.6-8 As many as one half of patients may be asymptomatic, and cases are often discovered incidentally as a result of routine chest radiography.2,3 In some patients, sarcoidosis appears for a period of 2 to 3 years and resolves, but 10 to 15% of patients may be chronically affected.7-9 Many cases are believed to resolve before they are recognized,6,7 but progression to fibrotic lung disease may occur. Some permanent lung damage occurs in approximately 20% of pulmonary cases, and the disease is fatal in 5 to 10% of cases in which either the granulomas or fibrosis seriously affect the function of a vital organ.9
Although a variety of environmental, occupational, infectious, and genetic risk factors have been suggested since the disorder was first documented in Europe 100 years ago, no single exposure has been found that accounts for the distribution of sarcoidosis.10 Sarcoidosis occurs in both sexes, all age groups, and all races.11- 13 In the United States, sarcoidosis is found most commonly among 20- to 40-year-old adults. Its prevalence is eight times higher among blacks, approaching 40 per 100,000, with prevalence among whites estimated at about 5 per 100,000.11-14 Sarcoidosis exhibits a high degree of familial aggregation, including across generations.15 There is also a mild genetic predisposition to sarcoidosis according to histocompatibility locus antigen type.16 Individuals of Scandinavian, German, Irish, or Puerto Rican origin also appear to be at greater than average risk.10
Sarcoidosis was once thought to be rare in North America, but a large number of cases were identified in the military beginning in the mid-1940s during annual chest radiographic screening.6 Annual screening led to several studies6,17-19 of sarcoidosis in military populations. These and other epidemiologic studies20-24 have identified a higher prevalence of sarcoidosis in individuals from the Southeast and rural areas of the United States, but few other risk factors. Due to the variability of symptoms, sarcoidosis diagnosis may be difficult and involves ruling out diseases with similar signs or symptoms.25
Although the identification of foreign bodies in granulomas is thought to exclude a diagnosis of sarcoidosis, an investigation26 using electron probe microanalysis found polarizable foreign bodies consisting of calcium, phosphorus, silicon, and aluminum in granulomatous skin lesions in some patients with cutaneous sarcoidosis. A foreign body may have served as an inciting stimulus for granuloma formation in some cases.26 Antibodies to cell wall- deficient organisms are not more prevalent in cases than control subjects.27 The short-term prognosis of sarcoidosis is highly variable.28
Sarcoid-like granulomas of the lung have been reported in individuals exposed to glass fibers or rockwool, which are composed of silicates.29 One case-control study30 found an odds ratio (OR) of 13.2 (95% confidence interval, 2.0 to 140.9) in individuals who were occupationally or environmentally exposed to crystalline silica from a plant that processed diatomaceous earth. Another study19 suggested a possible relationship of sarcoidosis with assignment aboard aircraft carriers, and with possible exposure to dust from removal of nonskid deck coating material, in particular. Particulate matter consisting of aluminum, titanium, silica, silicates, talc, iron, barium sulfate, and fibrous glass were identified in two samples of nonskid material of unknown origin.31 Among possibly exposed occupational groups, Navy boatswain’s mates assigned to aircraft carriers may have had the greatest potential exposure to nonskid coatings.
The objectives of this epidemiologic study were to examine the extent to which lung diseases other than sarcoidosis may have been misdiagnosed as sarcoidosis, and to evaluate the relationship between service in Navy enlisted occupational groups and incidence of hospitalized sarcoidosis. This study describes the incidence of sarcoidosis in active-duty Navy enlisted men according to race and occupational specialty.
MATERIALS AND METHODS
This study had an historical prospective study design. Information from military service records was extracted to determine incidence rates of hospitalized sarcoidosis among Navy enlisted men according to age, race, occupational specialty, and date. Incident cases of sarcoidosis, pneumoconioses, and other lung diseases were identified using the standard inpatient data record database of admissions to Department of Defense medical treatment facilities, provided by Tricare Management Activity, Washington, DC, from 1989 to 2001, and Navy hospitalization data sources from 1975 to 1988, before standard inpatient data record data were available. The Tricare Management Activity data were provided through the Executive Information/Decision System, which includes data on admissions to all military hospitals. Case ascertainment among active-duty Navy personnel included a broad range of lung disease diagnoses. Standard inpatient data records identified up to eight discharge diagnoses using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).32
Detailed population data during 1975 to 2001 were provided by the Defense Manpower Data Center, Monterey, CA. Age-specific incidence rates of first hospitalization for sarcoidosis, pneumoconioses, asthma, and other lung diseases were calculated according to race during 1975 to 2001. Race-specific standardized incidence ratios (SIRs) were used to compare age-adjusted hospitalized incidence rates in men by occupation and race. Records were merged into the Career History Archival Medical and Personnel System database of the Naval Health Research Center, creating a longitudinal record for each individual. Diagnoses ascertained were sarcoidosis (ICD-9-CM code 135), pneumoconioses (ICD-9-CM codes 501-505), asthma (ICD-9- CM code 493), emphysema and chronic bronchitis (ICD-9-CM codes 491- 492), and respiratory conditions due to dimes and vapors (ICD-9-CM code 506).
Incidence rates of first hospitalization for sarcoidosis, pneumoconioses, and other lung diseases were calculated according to age, race, and year of hospitalization. Person-years were aggregated across years, and midyear population counts were used fortime-trend analyses of incidence rates. Race-specific SIRs were used to compare age-adjusted rates by occupation and race.33 Age-specific sarcoidosis incidence rates for white or black Navy enlisted men were applied to the occupation-specific populations at risk stratified by race to yield race-specific SIRs for all 115 Navy enlisted occupations. Ninety-five percent confidence intervals were calculated using the Poisson distribution.34 These methods have been used to carry out previous epidemiologic studies of Navy service members.35-42
Annual age-specific incidence rates of lung disease based on first hospitalizations were calculated for black and white male personnel between 1975 and 2001. Incident hospitalized cases ascertained during this period included sarcoidosis (n = 674), asthma (n = 3,536), emphysema and chronic bronchitis (n = 1,103), respiratory conditions due to fumes and vapors (n = 61), and pneumoconioses (n = 51).
Annual incidence rates of hospitalized sarcoidosis peaked in whites at ages 35 to 39 years (6.9 per 100,000). The highest incidence rate among blacks was at 25 to 29 years (32.8 per 100,000). The overall average annual rate was 24.9 per 100,000 in black men and 3.5 in white men. The overall black/white ratio was 7.1 (p
In contrast to sarcoidosis, blacks had one half the incidence rate of pneumoconiosis in comparison to whites, although this difference was not statistically significant. A diagnosis of pneumoconiosis was rare in both races (Fig 1). The overall average annual incidence rate of asthma requiring hospitalization was higher in blacks (48.5 per 100,000) than whites (31.2 per 100,000), with an overall black/white ratio of 1.5 (p
FIGURE 1. Top: Annual incidence rates of first hospitalization for chronic lung disease, white active-duty enlisted men, US Navy, from 1975 to 2001. Bottom: Annual incidence rates of first hospitalization for chronic lung disease, black active-duty enlisted men, US Navy, from 1975 to 2001.
Annual incidence rates of sarcoidosis declined steeply from 1975 to 2001 in both white and black men (Fig 1), but the black/white ratio remained high throughout the study period. Sarcoidosis incidence rates dropped by about half among blacks after 1975, when a requirement for routine annual chest radiographs was eliminated. Incidence in blacks declined again after 1989, the year the Navy dropped its requirement for chest radiography at Navy entrance and separation (Fig 1). Pneumoconiosis rates were too low throughout the study period to account for the decline in sarcoidosis in either race.
Asthma was much more common than other chronic lung diseases in both whites and blacks during the study period, but asthma incidence did not appear to increase sufficiently among blacks during the study period to account for the contemporaneous decline in sarcoidosis incidence among blacks (Fig 1, bottom). The trend in incidence rates of emphysema and chronic bronchitis (COPD) in blacks also was not sufficient to explain a marked decline in sarcoidosis incidence among blacks (Fig 1, bottom).
Table 1-Occupations With Statistically Significantly High SIRs for Sarcoidosis in White or Black Navy Enlisted Personnel, January 1, 1975, to June 30, 2001*
Occupational associations were present among both white and black personnel (Table 1). Black ship’s servicemen and black aviation structural mechanics specializing in structures had slightly more than twice the expected incidence of sarcoidosis compared with all black male enlisted personnel. White mess management specialists also had twice the expected incidence of sarcoidosis in comparison with all white active-duty male enlisted personnel, with a similar trend in white ship’s servicemen.
Although its cause is unknown, several infectious agents and environmental factors have been associated with sarcoidosis.6,7,9- 13,20 Similar to respiratory infections, a diagnosis of sarcoidosis is more common during winter and early spring than during summer.22,24 Cases have been reported to cluster in certain geographic regions, and the disease is more common in rural areas21,23,43,44
Epidemiologic studies of sarcoidosis are difficult clue to the suspected high prevalence of undetected cases and the wide variety of other lung disorders with similar clinical presentations but different etiologies. For example, beryllium can produce a serious pulmonary disorder (berylliosis), which resembles sarcoidosis.45 Beryllium disease was recognized as the cause of a cluster of sarcoidosis-like pulmonary disease among young women employed in a fluorescent light factory.15 While there are sources of beryllium aboard some Navy ships, including metallic alloys and possibly some paints, it is unknown whether beryllium played any role in apparent cases of sarcoidosis in the present study. Aviation structural mechanics specializing in structures, who had higher than average SIRs, might possibly have been exposed during grinding of structural alloys. More recent studies described sarcoidosis-like pulmonary disease associated with exposure to silica compounds,29,30 photocopier toner dust,46 titanium dioxide,47,48 aluminum dusts,49,50 and zirconium.51
Pulmonary sarcoidosis is a clinical diagnosis based on symptomatology, radiographic features and, when available, microscopic examination of tissue. Criteria for pulmonary sarcoidosis in the Navy were similar to those in the civilian population (Robert Calloway, MD; personal communication; May, 2004).51,52 There generally was an expectation of a supportive radiograph with characteristic features, such as bilateral hilar lymphadenopathy, lung parenchymal infiltrates ascribable to sarcoidosis and not another cause, a negative tuberculin skin test result, and cough or dyspnea with no other explanation.53 If a biopsy was available, it was expected to contain noncaseating granulomas.
In the Navy population, as in the general population, pulmonary sarcoidosis was diagnosed mainly by a process of exclusion.5 Before 1975, many potential cases were detected with the characteristic radiographic appearance, and were referred for evaluation. In nonradiologically identified cases, and in general after 1975, the process of exclusion began with deciding whether the appropriate clinical picture was present. This would usually include longstanding cough in the absence of another cause, increasing dyspnea in the absence of a known cause, bilateral hilar adenopathy, interstitial lung disease, or both, and possibly rash, granulomata in skin, fever, uveitis, possibly cardiac rhythm changes, granulomata in a liver biopsy, hypercalcemia (depending on degree of ultraviolet exposure), or weight loss.
Whenever possible, bronchoscopy was performed to obtain a biopsy of lung epithelial tissue. Attempts were made to exclude known fungal diseases by cultures. Bronchoscopy was considered essential for making the final diagnosis of sarcoidosis in Navy personnel. It has been estimated that bronchoscopy was performed on approximately two thirds of active-duty servicemen who received a diagnosis of sarcoidosis, although definitive data are not available (Christopher T. Lewis, MD; personal communication; May, 2004). Bronchoscopy is recommended in most cases since diagnosis of sarcoidosis may be a cause for reassignment or, possibly, termination of service, and the diagnosis therefore has medicolegal implications. Biopsy findings in sarcoidosis cases generally included characteristic noncaseating granulomas.
The Navy has operated a centralized electronic record keeping system of data on all hospitalizations in Navy hospitals from 1966 through the present, known as the Career History Archival Medical and Personnel System.54 From 1975 to 1998, it included data on all hospitalizations, although not ambulatory care visits.
Intensive pre-enlistment screening is performed of all prospective military personnel, and includes a highly detailed medical history, obtained under oath. The pre-enlistment screening process excludes anyone with a history of sarcoidosis from military service, on the grounds that it is a progressive disease. Individuals with a chronic cough or dyspnea are given chest radiographs, and are excluded from service if there is bilateral hilar adenopathy or any other radiologie or clinical evidence of sarcoidosis.
The usual procedure during the 1960s and early 1970s was to hospitalize individuals with positive signs on mass screening chest radiographs for tuberculosis. When mass chest radiographic screening was discontinued by a Navy Medical Instruction in 1975, hospital admission for evaluation for sarcoidosis based solely on mass screening ceased.
Suspected pulmonary sarcoidosis patients were usually hospitalized for diagnosis and evaluation, since a chronic, progressive disease such as pulmonary sarcoidosis may be a basis for termination from military service, and the patient must be evaluated under controlled conditions. Since the mid-1980s, this policy has been modified somewhat, and evaluation is sometimes performed in an ambulatory care setting, except in severe symptomatic cases.
Since 1975, only individuals who were symptomatic, such as those with a persistent cough or a diagnosis of pneumonia, received chest radiographs (Robert Calloway, MD; personal communication; May, 2004). Since the late 1980s, an increasing proportion of referrals have been evaluated in an ambulatory care setting, including outpatient bronchoscopy. Increased use of outpatient bronchoscopy in the 1980s probably contributed to lower first hospitalization r\ates since the late 1980s.
Limited data were available on outpatient care for sarcoidosis. The rates of first ambulatory care visits for sarcoidosis from 1997 to 2003 were 27.2, 17.3, 19.3, 19.7, 14.5, 14.6, and 14.6 per 100,000 person-years, respectively. These are based on 94, 57, 61, 62, 46, 47, and 47 cases, respectively. These data suggest that first ambulatory care visits for sarcoidosis in the Navy may have declined somewhat during from 1997 to 2003. Rates of first ambulatory care visits in the Navy were lower than in other services. Rates in women also declined during this period (not shown). The source for the above ambulatory care data were the Defense Medical Epidemiology Database.
This study and earlier investigations19,54 found a substantially higher sarcoidosis incidence rate, based on first hospitalization rates, for Navy enlisted blacks than for whites, and a clear decline in hospitalized incidence rates for blacks over time.19,55 The average annual sarcoidosis incidence rate per 100,000 during from 1975 to 2000 was 21.9 for black men and 3.5 for white men. These were lower than the average annual incidence rates per 100,000 reported for black men (29.8) and white men (9.6) in Detroit, MI, during 1990 to 1994.14 Greater severity of the initial presentation in black cases may have resulted in a higher probability of hospitalization. If so, the high black/white ratio that was present for first hospitalization rates could be due, at least partly, to greater severity of the disease in blacks. However, the black/white ratio among ambulatory care visits was 5:1, suggesting that there was a black/white difference apart from any difference due to differential probability of hospitalization of blacks. In general, the lack of reliable population-based rates among US civilians makes these comparisons problematic. Higher prevalence of sarcoidosis among blacks remains unexplained but a disproportionate exposure to environmental or infectious agents, or a genetic predisposition, has been suggested.56
The present study is consistent with a previous case-control study of the Navy that reported high odds ratios for black race (OR, 8.6; 95% confidence limit [CL], 7.5 to 10.0), entry to the Navy before 1985 (OR, 4.7; 95% CL, 3.6 to 6.3), length of service (OR, 1.1 per year; 95% CL, 1.1 to 1.2), and age ≥ 20 years at entry (OR, 1.4; 95% CL, 1.3 to 1.7). The previous study did not provide ORs for occupations. It analyzed ORs whether the ship was considered “clean” or “dirty” from an inhalation viewpoint. The study found an OR of 0.06 (95% CL, 0.0 to 0.3) associated with assignments to only clean ships, among those assigned to Navy ships. After adjustment for race, the OR for assignment to exclusively clean ships was 0.33 (95% CL, 0.10 to 0.84). Most of the personnel aboard ships considered dirty were assigned aboard aircraft carriers, with a few aboard repair ships or other industrial-type ships. Clean ships included hospital ships, research ships, cargo carriers, and escort ships.
Findings from the present study are consistent with the findings of a previous study by Jajosky,19 including the present finding of a relative risk of approximated 2 associated with assignment to an aircraft carrier. The present study differed from the earlier study in that it used a cohort study design rather than a case-control approach, and examined trends in incidence in a broader range of pulmonary diseases than were examined in the previous study. The present study also analyzed associations with particular occupations not analyzed previously. The present study identified elevated incidence rates of sarcoidosis in ship’s servicemen, mess management specialists, and aviation structural mechanics that were not identified in the previous study.
In a previous article describing sarcoidosis hospitalizations among US Navy and Marine Corps personnel during 1981 to 1995, race, age, and enlisted status were significantly associated with a higher risk for sarcoidosis.55 Blacks had 7.5 times the risk of first hospitalization for sarcoidosis as whites, and age was positively associated with sarcoidosis risk. The highest rates of sarcoidosis admissions occurred before 1987. Rates appeared to drop dramatically beginning in 1988 and declined markedly through 1993.
The present study provides a further basis to investigate the reasons for the temporal decline in rates in the Navy. Although the decline in sarcoidosis incidence in the Navy may reflect unrecognized trends in the general population, other potential explanations include unknown secular changes that may be associated with risk. Pulmonary sarcoidosis symptoms may mimic symptoms of reactive airway disease.57 It is possible that some of the apparent decline in hospitalized sarcoidosis incidence in the Navy could be reflected in the increased incidence of asthma or other lung diseases with signs or symptoms similar to sarcoidosis over this time period.58 The Navy provides medical care to all personnel without charge. The same facilities and physicians provide care to personnel of all races and pay grades. The higher rate of first hospitalization for asthma in blacks in the Navy is intriguing, but the reasons are currently unknown. Although pulmonary sarcoidosis can be heralded solely by dyspnea or airways disease, it is unlikely to be misdiagnosed its asthma, due in part to differences in radiographic features.59,60 However, the lack of a contemporaneous increase in incidence of pneumoconiosis, asthma, or emphysema and chronic bronchitis is evidence against this explanation. It should be noted that diagnosis of emphysema or chronic bronchitis in individuals
Changes over time in work-related exposures cannot explain most of the declining trend. Only a few occupations were at high risk, and the degree of excess risk was moderate. Possibly relevant historical events included changes in formulations of nonskid materials and increased promotion of respirators and other measures designed to counter dust exposure. This study found occupational associations present among both white and black Navy enlisted personnel. For example, black aviation structural mechanics specializing in structures (12 cases) had approximately twice the expected incidence rate as those in other occupations (not shown). Aviation structural mechanics are routinely assigned to work aboard aircraft carriers, and could be expected to have had some degree of occupational exposure to nonskid material resulting from removal operations, or to alloys containing metals such as beryllium.
The strongest significant positive association with sarcoidosis was among black ship’s servicemen. According to interviews with veteran ship’s servicemen, these men operate laundry and dry cleaning operations aboard ships, and are barbers. Laundries are moist environments due the use of very hot water and steam. Dry cleaning requires use of solvents such as perchloroethylene. Until recent years, barbers were exposed to talc aerosols in powders. Ships’ servicemen serving as barbers also were possibly exposed to microscopic carbon particle aerosols from motors in hair trimmers. Mess management specialists cook and run kitchens, also in a moist, steamy work environment. Consistent with these findings, a previous study62 reported that exposure to moist environments was associated with increased risk of sarcoidosis.
Occupational assignment is a rough surrogate for any specific exposures that might be causally related to sarcoidosis or other lung diseases. However, the association of sarcoidosis with assignment to an aviation rating involving duty aboard aircraft carriers found in this and in a previous study19 suggests two possibilities. The first explanation is that a dust-related lung disease was erroneously diagnosed as sarcoidosis. The other explanation is that a previously unrecognized occupational association exists for sarcoidosis that was associated with service in an aviation rating. This possibility is worthy of further investigation, but would require better characterization of potential occupational exposures and environmental factors common to service in the occupation.
ACKNOWLEDGMENT: The authors thank the following individuals: Gary Hunninghake, MD, Chairman, Navy Lung Disease Assessment Program Scientific Advisory Council, Sarcoidosis Research Institute and Professor, Pulmonary Division, University of Iowa College of Medicine; Victor L. Roggli, MD, Chairman, Surgical Case Review Committee, Durham, VA Medical Center and Professor, Department of Pathology, Duke University School of Medicine; Mr. Jerry Cochran, Pastor, and Director, Jerry Cochran Veterans Outreach Foundation; Magdi Soliman, PhD, Professor of Pharmacology and Toxicology Program, Director, Environmental Health and Toxicology Research Program, Florida A&M University; Jerrold L. Abraham, MD, Director, Pathology Core Laboratory for the New York Occupational Health Clinics Network and Professor of Pathology, State University of New York at Syracuse, NY; Elaine B. Panitz, MD, MPH, Clinical Assistant Professor, Department of Medicine, Robert Wood Johnson Medical School, Piscataway, NJ; CAPT Garry Rudolph, Navy Bureau of Medicine and Surgery, Washington, DC; CAPT Richard Thomas, Navy Environmental Health Center, Norfolk, VA; Dr. Florabel Mullick, Principal Deputy Director, Armed Forces Institute of Pathology (AFIP), Washington, DC; CAPT David Trump, Uniformed Services University of the Health Sciences, Bethesda, MD; and Dr. Han Kang, Veterans Administration, Washington, DC. The authors thank Milan Miller and Dr. E.K. Eric Gunderson for data from the Career History Archival Medical and Personnel System at the Naval Health Research Center\, San Diego, CA, and CAPT Ken Capps from the Department of Clinical Investigations, Walter Reed Army Medical Center, Washington, DC, for his scientific-chemical review of case materials. We also thank Mike Dove and Scott Seggerman of the Defense Manpower Data Center, Monterey, CA, and Mariam Serra from the Department of Environmental and Toxicologic Pathology, AFIP, for technical assistance and provision of data, and Ms. Michele Cambou and Mr. Frankie Hasibuan at the Naval Health Research Center for data analysis.
* From the Naval Health Research Center (Drs. Gorham and F. C. Garland), San Diego, CA; Department of Family and Preventive Medicine (Dr. C. F. Garland), University of California, San Diego, La Jolla, CA; GEO-CENTERS, Inc. (Mr. Kaiser). Clinton, MD; and Armed Forces Institute of Pathology (Drs. Travis and Centeno), Washington, DC.
Report No. 02-20 was supported by the Navy Bureau of Medicine and Surgery, under work unit 60208. The views expressed in this report are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or US Government. Approved for public release; distribution unlimited. This research has been conducted in compliance with all applicable federal regulations governing the protection of human subjects in research.
1 Fanburg B, Lazarus D. Sarcoidosis. In: Murray J, Nadel J, eds. Textbook of respiratory medicine. 2nd ed. Philadelphia, PA: Saunders, 1994; 1873-1888
2 Katz S. Clinical presentation and natural history of sarcoidosis. In: Fanburg B, ed. Sarcoidosis and other granulomatous diseases of the lung. New York, NY: Marcel Dekker; 1983; 3-36
3 Keller AZ. Anatomic sites, age attributes, and rates of sarcoidosis in U. S. veterans. Am Rev Respir Dis 1973; 107:615-620
4 ACCESS Research Group. Design of a case control etiologic study of sarcoidosis (ACCESS). J Clin Epidemiol 1999; 52:1173-1186
5 Judson MA, Thompson BW, Rabin DL, et al. The diagnostic pathway to sarcoidosis. Chest 2003; 123:406-412
6 Sartwell PE, Edwards LB. Epidemiology of sarcoidosis in the U.S. Navy. Am J Epidemiol 1974; 99:250-257
7 James D, Turiaf I, Hosoda Y. Description of sarcoidosis: report of the subcommittee on classification and definition. Ann N Y Acad Sci 1976; 278:742
8 Sharma O, Bijwadia J. Monitoring and treating sarcoid lung disease. J Respir Dis 1993; 14:750-760
9 Keller AZ. Hospital, age, racial, occupational, geographical, clinical and survivorship characteristics in the epidemiology of sarcoidosis. Am J Epidemiol 1971; 94:222-230
10 Bresnitz EA, Strom BL. Epidemiology of sarcoidosis. Epidemiol Rev 1983; 5:124-156
11 Cummings MM, Dunner E, Williams JH Jr. Epidemiologic and clinical observations in sarcoidosis. Ann Intern Med 1959; 50:879- 890
12 Cummings MM, Dunner E, Schmidt RH Jr, et al. Concepts of epidemiology of sarcoidosis: preliminary report of 1,194 cases reviewed with special reference to geographic ecology. Postgrad Med 1956; 19:437-446
13 James DG. Epidemiology of sarcoidosis. Sarcoidosis 1992; 9:79- 87
14 Rybicki BA, Major M, Popovich J Jr, et al. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997; 145:234-241
15 Rybicki BA, Iannuzzi MC, Frederick MM, et al. Familial aggregation of sarcoidosis: a case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med 2001; 164:2085-2091
16 Rossman MD, Thompson B, Frederick M, et al. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003; 73:720-735
17 Cooch JW. Sarcoidosis in the United States Army, 1952 through 1956. Am Rev Respir Dis 1961; 84(5 Pt 2): 103-108
18 Gundelfinger BF, Britten SA. Sarcoidosis in the United States Navy. Am Rev Respir Dis 1961; 84(Pt 2):109-115
19 Jajosky P. Sarcoidosis diagnoses among U.S. military personnel: trends and ship assignment associations. Am J Prev Med 1998; 14:176-183
20 Israel HL. Influence of race and geographical origin on sarcoidosis. Arch Environ Health 1970; 20:608-609
21 Siltzbach LE. Geographic aspects of sarcoidosis. Trans N Y Acad Sci 1967; 29:364-374
22 Bardinas F, Morera J, Fite E, et al. Seasonal clustering of sarcoidosis. Lancet 1989; 2:455-456
23 Gentry JT, Nitowsky HM, Michael M Jr. Studies on the epidemiology of sarcoidosis in the United States: the relationship to soil areas and to urban-rural residence. J Clin Invest 1955; 34:1839-1856
24 Bresnitz EA, Stolley PD, Israel HL, et al. Possible risk factors for sarcoidosis: a case-control study. Ann N Y Acad Sci 1986; 465:632-642
25 Hennessy TW, Ballard DJ, DeRemee RA, et al. The influence of diagnostic access bias on the epidemiology of sarcoidosis: a population-based study in Rochester, Minnesota, 1935-1984. J Clin Epidemiol 1988; 41:565-570
26 Kim YC, Triffet MK, Gibson LE. Foreign bodies in sarcoidosis. Am J Dermatopathol 2000; 22:408-412
27 Brown ST, Brett I, Almenoff PL, et al. Recovery of cell wall- deficient organisms from blood does not distinguish between patients with sarcoidosis and control subjects. Chest 2003; 123:413-417
28 Judson MA, Baughman RP, Thompson BW, et al. Two year prognosis of sarcoidosis: the ACCESS experience. Sarcoidosis Vasc Diffuse Lung Dis 2003; 20:204-211
29 Drent M, Bomans PH, Van Suylen RJ, et al. Association of man- made mineral fibre exposure and sarcoidlike granulomas. Respir Med 2000; 94:815-820
30 Rafnsson V, Ingimarsson O, Hjalmarsson I, et al. Association between exposure to crystalline silica and risk of sarcoidosis. Occup Environ Med 1998; 55:657-660
31 Abraham J, Panitz E. Is sarcoidosis in the U.S. Navy occupational lung disease from the grinding of nonskid paint aboard aircraft carriers? Analysis of inorganic particulars in lungs and a reference paint sample [abstract]. Am J Respir Crit Care Med 1991; 163:A214
32 International Classification of Diseases, Ninth Revision, Clinical Modification, Salt Lake City, UT: Medicode, 1998
33 Fleiss J. Statistical methods for rates and proportions. New York, NY: Oxford, 1981
34 Lilienfeld D, Stolley P. Foundations of epidemiology. 3rd ed. New York, NY: Oxford, 1994
35 Garland FC, Gorham ED, Garland CF. Hodgkin’s disease in the US Navy. Int J Epidemiol 1987; 16:367-372
36 Garland F, Gorham E, Garland C. Non-Hodgkin’s lymphomas in U.S. nasal personnel. Arch Environ Health 1988; 43:425-429
37 Garland F, Gorhani E, Garland C, et al. Testicular cancer in US Navy personnel. Am J Epidemiol 1988; 127:411-414
38 Garland F, Shaw E, Gorham E, et al. Incidence of leukemia in occupations with potential electromagnetic field exposure in United States Navy personnel. Am J Epidemiol 1990; 132:293-303
39 Garland F, White M, Garland C, et al. Occupational sunlight exposure and melanoma in the U.S. Navy. Arch Environ Health 1990; 45:261-267
40 Garland F, Gorham E, Cunnion S, et al. Decline in human immunodeficiency virus seropositivity and seroconversion in U.S. Navy enlisted personnel: 1986-1989. Am J Pub Health 1992; 82:581- 584
41 Gorham E, Garland F, Barrett-Connor E, et al. Incidence of insulin-dependent diabetes mellitus in young adults: experience of 1,587,630 U.S. Navy enlisted personnel. Am J Epidemiol 1993; 138:984- 987
42 Garland FC, Garland CF, Doyle EJ Jr, et al. Carpal tunnel syndrome and occupation in U.S. Navy enlisted personnel. Arch Environ Health 1996; 51:395-407
43 Kajdasz DK, Lackland DT, Mohr LC Jr, et al. A current assessment of rurally linked exposures as potential risk factors for sarcoidosis. Ann Epidemiol 2001; 11:111-117
44 Kajdasz DK, Judson MA, Mohr LC Jr, et al. Geographic variation in sarcoidosis in South Carolina: its relation to socioeconomic status and health care indicators. Am J Epidemiol 1999; 150:271-278
45 Newman LS, Kreiss K, King TE Jr, et al. Pathologic and immunologic alterations in early stages of beryllium disease: re- examination of disease definition and natural history. Am Rev Respir Dis 1989; 139:1479-1486
46 Armbruster C, Dekan G, Hovorka A. Granulomatous pneumonitis and mediastinal lymphadenopathy due to photocopier toner dust [letter]. Lancet 1996; 348:690
47 Pimentel JC. Systemic granulomatous disease, of the sarcoid type, caused by inhalation of titanium dioxide: anatomoclinical and experimental study. Acta Med Port 1992; 5:307-313
48 Redline S, Barna BP, Tomashefski JF Jr, et al. Granulomatous disease associated with pulmonary deposition of titanium. Br J Ind Med 1986; 43:652-656
49 De Vuyst P, Dumortier P, Schandene L, et al. Sarcoid-like lung granulomatosis induced by aluminum dusts. Am Rev Respir Dis 1987; 135:493-497
50 Hull MJ, Abraham JL. Aluminum welding fume-induced pneumoconiosis. Hum Pathol 2002; 33:819-825
51 Kotter JM, Zieger G. Sarcoid granulomatosis after many years of exposure to zirconium, “zirconium lung”. Pathologe 1992; 13:104- 109
52 Thrasher DR, Briggs DD Jr. Pulmonary sarcoidosis. Clin Chest Med 1982; 3:537-563
53 Patchefsky A. Non-neoplastic pulmonary disease. In: Sternberg S, ed. Diagnostic surgical pathology. New York, NY: Raven Press, 1989; 715-784
54 Gunderson E, Miller M, Garland C. Career History Archival Medical and Personnel System. Mil Med 2005 (in press)
55 McDonough C, Gray GC. Risk factors for sarcoidosis hospitalization among U.S. Navy and Marine Corps personnel, 1981 to 1995. Mil Med 2000; 165:630-632
56 Centers for Disease Control. Sarcoidosis among U.S. Navy enlisted men, 1965-1993. MMWR Morb Mortal Wkly Rep 1997; 46:539-543
57 Pesola GR, Kurdi M, Olibrice M. Endobronchial sarcoidosis and hyperreactive airways disease [letter]. Chest 2002; 121:2081
58 Connolly JP, Baez SA. Asthma in the Navy and Marine Corps. Mil Med 1991; 156:461-465
59 Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164(10 pt 1):1885-1889
60 Bauer HJ, Wijkstrom S. The prevalence of pulmonary sarcoidosis in Swedish mass radiography surveys. Acta Med Scand Suppl 1964; 425:112-1\14
61 Lange P, Parner J, Prescott E, et al. Chronic bronchitis in an elderly population. Age Ageing 2003; 32:636-642
62 Kucera GP, Rybicki BA, Kirkey KL, et al. Occupational risk factors for sarcoidosis in African-American siblings. Chest 2003; 123:1527-1535
Edward D. Gorham, MPH, PhD; Cedric F. Garland, DrPH; Frank C. Garland, PhD; Kevin Kaiser, MPH; William D. Travis, MD, FCCP; and Jose A. Centeno, PhD
Manuscript received January 30, 2004; revision accepted June 18, 2004.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: firstname.lastname@example.org).
Correspondence to: Edward D. Gorham, MPH, PhD, Naval Health Research Center, PO Box 85122, San Diego, CA 92186-5122; e-mail: email@example.com
Copyright American College of Chest Physicians Nov 2004