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* 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.
Correspondence to: Edward D. Gorham, MPH, PhD, Naval Health Research Center, PO Box 85122, San Diego, CA 92186-5122; e-mail: gorham{at}nhrc.navy.mil
| Abstract |
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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 < 0.0001). Annual incidence rates in blacks declined markedly, particularly since 1989, but the black/white ratio remained high through 1999. Occupational associations were present in blacks and whites. Black ships servicemen (23 cases) and aviation structural mechanics specializing in structures (12 cases) had more than twice the expected incidence rate compared to all blacks, and white mess management specialists (15 cases) had twice the overall white incidence rate.
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.
Key Words: epidemiology military populations occupation occurrence sarcoidosis
| Introduction |
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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.111213 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 100,000.11121314 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 studies6171819 of sarcoidosis in military populations. These and other epidemiologic studies2021222324 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 boatswains 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 |
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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 501505), asthma (ICD-9-CM code 493), emphysema and chronic bronchitis (ICD-9-CM codes 491492), and respiratory conditions due to fumes and vapors (ICD-9-CM code 506).
Statistical Analysis
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 for time-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.3536373839404142
| Results |
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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 < 0.0001).
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 < 0.0001) [Fig 1]. Hospitalized cases of emphysema and chronic bronchitis were twice as common in whites (12.0 per 100,000) as blacks (5.9 per 100,000; p < 0.0001) [Fig 1]. First hospitalization for lung injuries due to inhalation of fumes and vapors were equally common among blacks and whites, with overall incidence rates of 0.6 per 100,000 in both.
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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).
Occupational associations were present among both white and black personnel (Table 1 ). Black ships 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 ships servicemen.
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| Discussion |
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Epidemiologic studies of sarcoidosis are difficult due 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.45 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,2930 photocopier toner dust,46 titanium dioxide,4748 aluminum dusts,4950 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).5152 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 radiologic 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 rates 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 investigations1954 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.1955 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 approximately 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 ships 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 as asthma, due in part to differences in radiographic features.5960 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 < 45 years old, such as most of the Navy enlisted population, should be regarded with a degree of caution, since this disease is most prevalent in older adults with long-term cigarette smoking histories.61
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 ships servicemen. According to interviews with veteran ships 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.
| Acknowledgements |
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| Footnotes |
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Report No. 0220 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.
Received for publication January 30, 2004. Accepted for publication June 18, 2004.
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