Abstract
Background
Lymph node silicosis (LNS) may be found when investigating lung and mediastinal diseases. Co-occurrence of LNS and pulmonary silicosis (PS) has been described but no studies have investigated the diagnostic accuracy of LNS for PS, the aim of this study.
Methods
This cross-sectional study included South African miners with exclusive gold-mining employment who had autopsy examinations from 1975 to 2018. Routinely recorded pathologist-diagnosed LNS and PS and occupational histories were retrieved from the PATHAUT database. Pulmonary silicosis was the reference standard. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and summary diagnostic accuracy were calculated overall and by PS severity and employment duration.
Results
Of the 69 802 miners, the prevalences of LNS and PS were 39.2% (n=27 373) and 17.7% (n=12 345), respectively. There were 24.1% false-positive LNS tests. Sensitivity was 85.2% (95% CI 84.6–85.6), but specificity was lower (70.7%, 95% CI 70.3–71.0). The PPV and NPV were 38.4% (95% CI 37.9–39.0) and 95.7% (95% CI 95.5–95.9), respectively. Sensitivity increased and specificity decreased with increasing employment duration.
Conclusions
Our findings are consistent with LNS occurring at concentrations of respirable crystalline silica too low to cause PS and possibly being a portent of PS. LNS had deficits as a diagnostic test for PS. The low PPV raises uncertainty about the presence of PS in patients with LNS. LNS may perform better in populations with higher prevalence of silicosis, for example in patients with clinically suspected PS.
Shareable abstract
Incidental findings of lymph node silicosis (LNS) occur. LNS and pulmonary silicosis (PS) co-occur often. While LNS findings may not be useful for PS diagnosis, they should prompt patient and workplace investigations for PS and silica exposures. https://bit.ly/3CKz43F
Introduction
Mediastinal and hilar lymph node silicosis (LNS) is the presence of silicotic nodules in these nodes. The nodules are the same histologically as those found in the lung itself, a disease we term pulmonary silicosis (PS) to distinguish it from LNS. Both conditions are caused by the inhalation of respirable crystalline silica (RCS), a hazard encountered in numerous workplaces and in some intensely dusty general environments [1]. Mining in South Africa has caused thousands of cases of silicosis since the inception of mining in the late 1800s [2].
Lymph node biopsy has become easier and safer using endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) or EBUS-guided transbronchial mediastinal cryobiopsy. These procedures are minimally invasive but highly effective in the diagnosis and staging of lung cancer, but also benign disorders [3–6]. These techniques are likely to be valuable in the diagnosis of pathologic reactions to RCS. Published case series have supported the potential clinical value of EBUS-TBNA. Shitrit et al. (2018) [7] wrote that “EBUS-TBNA is a useful and sufficient tool to diagnose silicosis in patients with mediastinal lymphadenopathy along [with] compatible exposure histories.”. In two other case studies, EBUS-TBNA was used to investigate patients with suspect silicosis, successfully, according to the researchers [8, 9]. These studies were small, however, and the data provided are insufficient to assess the associations between LNS and PS.
The incidental identification of LNS may not be infrequent given the large numbers of patients undergoing lymph node EBUS and sizeable silica-exposed populations globally, including those in the artificial stone industry, in whom LNS has been identified [10]. EUS-TBNA is used globally including in populous middle-income countries such as Brazil [11], China [12], India [13] and Malaysia [14]. These and other countries have millions of silica-exposed individuals and large numbers of cases of silicosis [1]. Thus, the need to interpret the presence of LNS with respect to PS may arise.
It has been long recognised that computed tomography (CT) is more sensitive than chest radiography in the detection of PS [15]. This increased sensitivity has been confirmed using modern CT techniques [16, 17]. The sensitivity of CT relative to histology is, however, unknown. It is possible that LNS could be found in patients without the typical imaging features of silicosis. Thus, the diagnostic accuracy of LNS remains of interest in patients who have had CT.
In two cross-sectional studies, lymph node fibrosis and LNS occurred at lower cumulative silica exposures than those causing PS [18, 19]. Lymph node-only fibrosis or silicosis was more common than PS at low cumulative silica exposures and the proportion of individuals with co-occurrence of lymph node fibrosis or silicosis and PS increased with increasing cumulative exposure categories. These findings are consistent with LNS preceding PS, possibly due to RCS damage to the nodes promoting the development of PS [18–21]. LNS may, therefore, signal future PS [18] and could be used as a silica-associated disease prevention signal.
The South African Occupational Disease in Mines and Works Act makes provision for compensation for autopsy-diagnosed occupational lung diseases in miners [22]. Since 1975, pathological findings, including routine reporting of LNS and PS, personal information and mining histories have been stored in the electronic PATHAUT (Pathology Automation System) database [23]. In 2018, PATHAUT contained over 110 000 records [24]. PATHAUT thus contains large numbers of appropriate records to examine the diagnostic accuracy of LNS for PS, the aim of this study. Additionally, the study examined whether gold-mining employment duration, a proxy of the extent of RCS exposure, influenced diagnostic accuracy.
Methods
In this cross-sectional study, all miners in the PATHAUT database (1975 to 2018) with exclusive gold-mining employment, irrespective of duration, were selected.
Pathology examination
With consent from the next of kin and regardless of the clinical cause of death, the cardiorespiratory organs of miners are removed locally where death occurs, placed in formalin and transported to the National Institute for Occupational Health (NIOH) in Johannesburg. These organs are examined by pathologists experienced in mining-related disorders using standardised criteria for the diagnosis and, where appropriate, determination of the severity of occupational lung diseases.
Routinely, the lungs are examined visually and thoroughly palpated for nodules. Tissue sections are taken from the upper, middle and lower zones of each lung, the right main bronchus, heart and the right and left hilar lymph nodes. Firm nodes are purposely selected. The sections are stained with haematoxylin and eosin for histological examination.
During macroscopic examination, the degree of PS is graded according to the number of palpable silicotic nodules in the right lung, as follows: none, occasional (1–4 nodules), few (5–14 nodules), moderate (15–30 nodules) and marked (more than 30 nodules). The presence of LNS and PS is confirmed histologically as the presence of fibrotic nodules of whorled, concentric thick acellular collagen fibres. The severity of LNS is not graded and is recorded as present or absent.
Progressive massive fibrosis (PMF) is diagnosed as coalescent silicotic nodules forming a focus of fibrosis ≥2 cm in its largest dimension. This was the workers’ compensation standard at the time of data collection for this study.
Occupational history
In PATHAUT, each miner's employment history is categorised based on information obtained from mine employment records. Commodity (type of mineral mined) and employment duration in each commodity were used. RCS measurements for individual miners are not captured in PATHAUT, hence gold-mining employment duration was used as a proxy for RCS exposure.
Study variables
Personal information (year of death and age), occupational information (commodity and employment duration) and silicosis-related pathology findings were obtained from PATHAUT. Age and gold-mining employment duration were grouped into 10-year categories. LNS and PS were defined as binary variables (present or absent) and the severity of PS was categorised into five grades with increasing severity: occasional, few, moderate and large numbers of nodules and progressive massive fibrosis. The co-occurrence of LNS and PS was defined as the number of miners who had silicosis in both sites (true positives) as a proportion of the total miners with LNS and/or PS.
Data analysis
Statistical analyses were conducted in Stata v. 18 (StataCorp, College Station, TX, USA). Categorical variables were summarised using frequencies and percentages and continuous variables as mean±sd. A t-test and chi-square tests for trend were used to determine statistically significant differences between groups for continuous and categorical variables, respectively.
PS was the reference standard in all diagnostic accuracy calculations. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and summary diagnostic accuracy, also known as diagnostic effectiveness, were calculated using standard formulae [25]. Summary diagnostic accuracy provides a measure of correctly classified cases (true positives and true negatives as a proportion of the total population). Diagnostic accuracy calculations were also done for PS severity and gold employment duration categories. Calculations were performed using the conftab and diagt ado files in Stata.
Ethical considerations
Ethical approval for the study was obtained from the University of the Witwatersrand, Human Research Ethics Committee (Medical) (clearance certificate number M220564).
Results
Of the 113 501 records in PATHAUT (1975 to 2018), 69 802 miners with exclusive gold-mining employment were included in the analyses (table 1).
TABLE 1.
Numbers of miners in the PATHAUT database and numbers excluded from the study, 1975 to 2018
| Records in PATHAUT | N=113 501 | |
|---|---|---|
| Exclusion criteria | Number excluded | Number remaining |
| Employment in commodity other than gold | 40 616 | 72 885 |
| Age not stated | 2810 | 70 075 |
| Insufficient lung tissue for examination | 272 | 69 802 |
PATHAUT: Pathology Automation System.
Over the study period, LNS was diagnosed in 27 373 (39.2%) gold miners and PS in 12 345 (17.7%). The annual proportions of both conditions increased over time (figure 1). From 1975 to 2018, PS increased from 10.1% to 27.3% and LNS from 34.7% to 55.6%. The dip in 1996 was due to administrative changes that interrupted data capture [26]. Throughout the study period, the annual proportions of miners with LNS were higher than those of PS. We used data presented in figure 1 to calculate the ratios of LNS to PS (results not shown). The ratios decreased from 3.5 in 1975 to 2.7 in 1985, 2.0 in 1995, 1.8 in 2005, and 2.0 in 2015 and 2018.
FIGURE 1.
Annual proportions of lymph node and pulmonary silicosis in 69 802 deceased South African gold miners, 1975 to 2018.
Miners with PS were significantly older (p<0.001) than those without PS, (56.0±13.8 years and 43.5±13.8 years, respectively) and had significantly (p<0.001) longer gold-mining employment duration (21.0±12.1 years and 11.2±11.6 years, respectively) (results not presented in tables). The distributions presented in table 2 are frequencies and proportions of the total miners with (n=12 345) and without PS (n=57 457). Occasional nodules, indicating mild disease, were found in 43.2% of the miners with PS. The proportions of miners decreased with increasing PS severity with fewer miners having marked silicosis (n=847, 6.9%) and progressive massive fibrosis (n= 575, 4.7%). Most cases of PS had LNS; of the 12 345 miners with PS, 10 520 (85.2%) had LNS.
TABLE 2.
Characteristics of gold miners by status of pulmonary silicosis diagnosed at autopsy, 1975 to 2018.
| Characteristic | Pulmonary silicosis present, n=12 345 (17.7%) | Pulmonary silicosis absent, n=57 457 (82.3%) | Total n=69 802 (100%) |
|---|---|---|---|
| n (%) | n (%) | n | |
| Age group, years | |||
| <30 | 89 (0.7) | 11 733 (20.4) | 11 822 |
| 30–39 | 1012 (8.2) | 15 352 (26.7) | 16 364 |
| 40–49 | 3615 (29.3) | 12 486 (21.7) | 16 101 |
| 50–59 | 3192 (25.9) | 7913 (13.8) | 11 105 |
| 60–69 | 1941 (15.7) | 5163 (9.0) | 7104 |
| ≥70 | 2496 (20.2) | 4810 (8.4) | 7306 |
| Gold service duration group, years | |||
| 0.1–9 | 1291 (10.5) | 22 454 (39.1) | 23 745 |
| 10–19 | 3365 (27.3) | 12 752 (22.2) | 16 117 |
| 20–29 | 3368 (27.3) | 6337 (11.0) | 9705 |
| 30–39 | 2593 (21.0) | 4361 (7.6) | 6954 |
| ≥40 | 648 (5.2) | 1371 (2.4) | 2019 |
| Not stated | 1080 (8.7) | 10 182 (17.7) | 11 262 |
| Pulmonary silicosis severity | |||
| Occasional | 5330 (43.2) | 0 (0) | 5330 |
| Few | 2917 (23.6) | 0 (0) | 2917 |
| Moderate | 2676 (21.7) | 0 (0) | 2676 |
| Marked | 847 (6.9) | 0 (0) | 847 |
| Progressive massive fibrosis | 575 (4.7) | 0 (0) | 575 |
| Lymph node silicosis | |||
| Present | 10 520 (85.2) | 16 853 (29.3) | 27 373 |
| Absent | 1825 (14.8) | 40 604 (70.7) | 42 429 |
Co-occurrence
The overall co-occurrence of LNS and PS was 36.0% (figure 2). Co-occurrence increased with increasing PS severity from 79.9% in miners with occasional silicotic islets to 91.0% in those with marked silicosis (figure 2). Co-occurrence increased from 20.5% in miners with 0.1–9 years of employment to 46.2% in miners with 30–39 years of employment (figure 3). The increases were accompanied by decreased proportions of LNS only (73.4% to 49.2%), whereas the PS-only proportions remained fairly constant (4.6–7.3%). Of the 57 457 miners without PS, 29.3% (n=16 853) had LNS.
FIGURE 2.
Venn diagram of lymph node silicosis (LNS) only, co-occurrence of LNS and pulmonary silicosis (PS) and PS only, overall and by severity of PS.
FIGURE 3.
Venn diagram of lymph node silicosis (LNS) only, co-occurrence of LNS and pulmonary silicosis (PS) and PS only by duration of gold-mining employment.
Diagnostic accuracy
Measures of diagnostic accuracy using PS as the reference standard are shown in table 3. The proportions of true positives increased significantly (p<0.001) with increasing PS severity from 79.9% in those with occasional islets to 91.0% and 89.3% in those with marked PS and progressive massive fibrosis (PMF), respectively. Conversely, the proportions of false-negative diagnoses were lower and decreased with increasing PS severity from 20.1% in miners with occasional nodules to 5.6% in those with PMF (p<0.001).
TABLE 3.
Measures of diagnostic accuracy of lymph node silicosis for pulmonary silicosis in 69 802 South African gold miners
| Characteristic | True positive (LNS+/PS+) |
False negative (LNS−/PS+) |
False positive (LNS+/PS−) |
True negative (LNS−/PS−) |
Total | Sensitivity | Specificity | PPV | NPV | Accuracy |
|---|---|---|---|---|---|---|---|---|---|---|
| n (%)# | n (%) | n (%) | n (%) | % (CI) | % | % | % | % | ||
| All miners | 10 520 (15.1) | 1825 (2.6) | 16 853 (24.1) | 40 604 (58.2) | 69 802 | 85.2 (84.6–85.6) | 70.7 (70.3–71.0) | 38.4 (37.9–39.0) | 95.7 (95.5–95.9) | 73.2 |
| PS severity | ||||||||||
| Absent | 0 (0) | 0 (0) | 16 825 (29.3) | 40 601 (70.7) | 57 426 | NA | NA | NA | NA | NA |
| Occasional | 4258 (79.9) | 1072 (20.1) | 0 (0) | 0 (0) | 5330 | NA | NA | NA | NA | NA |
| Few | 2579 (88.4) | 338 (11.6) | 0 (0) | 0 (0) | 2917 | NA | NA | NA | NA | NA |
| Moderate | 2371 (88.6) | 305 (11.4) | 0 (0) | 0 (0) | 2676 | NA | NA | NA | NA | NA |
| Large number | 771 (91.0) | 76 (9.0) | 0 (0) | 0 (0) | 847 | NA | NA | NA | NA | NA |
| PMF | 541 (89.3) | 34 (5.6) | 28 (4.6) | 3 (0.5) | 606 | NA | NA | NA | NA | NA |
| Gold employment duration group, years | ||||||||||
| 0.1–9 | 995 (4.2) | 296 (1.2) | 3561 (15.0) | 18 893 (79.6) | 23 745 | 77.1 (74.7–79.3) | 84.1 (83.7–84.6) | 21.8 (20.6–23.1) | 98.5 (98.3–98.6) | 83.8 |
| 10–19 | 2784 (17.3) | 581 (3.6) | 4635 (28.8) | 8117 (50.4) | 16 117 | 82.7 (81.4–84.0) | 63.6 (62.8–64.5) | 37.5 (36.4–38.6) | 93.3 (92.8–93.8) | 67.6 |
| 20–29 | 2964 (30.5) | 404 (4.2) | 3248 (33.5) | 3089 (31.8) | 9705 | 88.0 (86.9–89.1) | 48.8 (47.5–50.0) | 47.7 (46.5–49.0) | 88.4 (87.3–89.5) | 62.4 |
| 30–39 | 2358 (33.9) | 235 (3.4) | 2512 (36.1) | 1849 (26.6) | 6954 | 90.9 (89.8–92.0) | 42.4 (40.9–43.9) | 48.4 (47.0–49.8) | 88.7 (87.3–90.1) | 60.5 |
| ≥40 | 588 (29.1) | 60 (3.0) | 798 (39.5) | 573 (28.4) | 2019 | 90.7 (88.2–92.9) | 41.8 (39.2–44.5) | 42.4 (39.8–45.1) | 90.5 (88.0–92.7) | 57.5 |
| Not stated | 831 (7.4) | 249 (2.2) | 2099 (18.6) | 8083 (71.8) | 11 262 | 76.9 (74.3–79.4) | 79.4 (78.6–80.2) | 28.4 (26.7–38.0) | 97.0 (96.6–97.4) | 79.2 |
LNS: lymph node silicosis; PS: pulmonary silicosis; +: present; −: absent; PPV: positive predictive value; NPV: negative predicted value; CI: 95% confidence interval; PMF: progressive massive fibrosis; NA: not available. Accuracy: true positives+true negatives/total number of miners. #: Percentages are calculated as row proportions (n/category total).
The proportions of true-positive diagnoses increased with increasing employment duration from 4.2% (0.1–9.0 years of employment) to 29.1% (≥40 years) (p<0.001). Miners with the fewest years of mining had the lowest proportion of false negatives: PS was less common in these cases (n=1291, 10.5%). False-negative diagnoses increased from 1.2% (0.1–9.0 years of employment) to 4.2% (20–29 years) and decreased thereafter. False-negative diagnoses were most common in miners with occasional nodules (mild silicosis) (n=1072, 20.1%) but declined as severity increased.
The sensitivity of LNS for PS was 85.2%, reflecting the high proportion of miners with PS who had LNS. Specificity was lower (70.7%) indicating that 29.3% of miners without PS did not have LNS. The PPV was low at 38.4% showing that many miners who were LNS positive did not have PS. The NPV was much higher than the PPV at 95.7% suggesting that LNS absence strongly indicated PS absence. The summary diagnostic accuracy of 73.2% means that LNS presence or absence incorrectly labelled about 27% of miners with or without PS.
Increasing years of employment produced a modest increase in sensitivity, but a more marked decline in specificity, reaching a low of 41.8% with ≥40 years of employment (table 3). Comparing PPV and NPV across employment categories is problematic because prevalence varied by employment category (table 2), and disease prevalence is known to affect these parameters [22]. The PPV remained under 50%. NPV was above 88% for all employment duration categories and was highest (98.5%) for workers with short employment. Summary diagnostic accuracy, also affected by prevalence, was only about 60% after 20–29 years of employment suggesting that approximately 40% of LNS diagnoses would incorrectly indicate the presence or absence of PS in long employment workers.
Discussion
Our study evaluated the diagnostic accuracy of autopsy-diagnosed LNS for PS in a large population of 68 902 South African gold miners. We found that LNS had deficits for diagnostic accuracy for PS.
The overall proportions of LNS and PS were high: 39.2% and 17.7%, respectively. The observed increases in silicosis over time have been shown to be associated with increasing employment duration and age of miners [2, 20]. The annual proportions of miners with LNS were higher than those of PS throughout the four-decade study period. As PS increased, the co-occurrence of LNS and PS became more likely.
In approximately a quarter of miners (24.1%), LNS occurred in the absence of PS (false positives). This finding is consistent with LNS occurring at RCS concentrations too low to cause PS. This has been described previously in cumulative RCS exposure studies [18, 19]. These findings are also compatible with LNS being a portent of PS in some, possibly many, of these miners.
Contrary to the hypothesis of LNS preceding PS is the finding that 14.8% of miners with PS did not have LNS. This contrary finding may, however, have occurred because of the small number of lymph nodes sampled from each miner: missed LNS is a reasonable explanation for false-negative (LNS−/PS+) cases.
The sensitivity of LNS for PS was good at 85.2% (i.e. LNS identified a high proportion of miners with PS). LNS, however, had deficits as a tool to diagnose PS. In 24.1% of the miners without PS, LNS was present (i.e. a false-positive LNS test). Specificity was lower at 70.7%, indicating that LNS failed to label 29.3% of those without PS negative.
The low PPV (38.4%) was the most problematic measure of diagnostic accuracy. This low PPV means that in this population, LNS was poor at identifying PS in individual cases. Clinicians and others (e.g. workers’ compensation adjudicators) would be uncertain about the presence of PS in a patient with positive LNS. The PPV was <50% in all employment duration categories, even those with long service. More favourably, the absence of LNS combined with short mining employment (0.1–9 years) effectively ruled out silicosis in these cases (NPV of 98.5%).
LNS incidentally diagnosed by EBUS investigation of patients will occur, especially in countries with large RCS-exposed populations. Despite the deficits in the diagnostic accuracy of LNS for PS the finding of LNS may still be useful. For example, subradiological silicosis (silicosis inapparent on the chest radiograph) is common [27]. The detection of LNS in patients without obvious silicosis on chest radiograph could prompt the taking of a RCS exposure history and enhanced imaging with, for example, CT. LNS is a signal of a pathological response to RCS and should lead to evaluations of workplace exposure and RCS controls.
To our knowledge, there are no other studies on the diagnostic accuracy of LNS for PS. Directly relating our findings to those of comparable studies is, therefore, not possible. Other studies have, however, examined the associations between LNS and PS. Taeger et al. (2011) [19] found about half (12.9%) the proportion of false-positive diagnoses (lymph node-only silicosis) in 4384 German uranium miners with lung cancer than the 24.1% in our study. The lower proportion of false positives in the German uranium miner study may be explained by higher RCS exposures and higher silicosis prevalence (53.6% compared with 17.7% in our study) [19]. An earlier study of 264 uranium miners in Germany [18] had a higher but similar false-positive proportion as our study: 33.5% and 24.1%, respectively. In the same study [18], the proportions of true positive (90.3% and 85.2%) and false negative (9.6% versus 14.8%) were comparable with those in our study. Different RCS exposures and silicosis prevalences would explain some of the variation in the two populations.
Early markers of pathological responses to RCS or silicosis – a disease typically of long latency difficult to detect early, treat and prevent disease progression – are needed but are unavailable. Other than LNS, there is interest in validating molecular biomarkers for silicosis as indicators of hazardous exposure, population risk and disease, especially early disease. Several methods have been explored [28], and one (club cell secretory protein; CC16) is a point-of-care kit [29]. Presently the biomarkers have limitations [28] and no individual biomarker has been shown to be sufficiently sensitive and specific for silicosis to be useful in clinical settings, although there is potential [30].
Strengths and limitations
A strength of our study is the use of PATHAUT, a long-established source of data for many important studies of cardiorespiratory disorders, including silicosis and RCS-associated diseases [20, 26, 31]. The data are generated by specialist anatomical pathologists experienced in mining-related disorders and, in addition to internal validation processes, the autopsy diagnoses of silicosis, pulmonary tuberculosis and coal workers pneumoconiosis, and emphysema have been externally validated [32]. The large study sample, 69 802 gold miners with RCS exposure, is unprecedented. Thus, the measures of diagnostic accuracy are highly likely to be reliable for this and similar populations.
Limitations include the cross-sectional design of our study. We were unable to determine the extent to which LNS is an antecedent of PS as we could not ascertain the proportion with lymph node-only silicosis who went on the develop PS. This would require a cohort study which is methodically and logistically difficult.
There may have been some diagnostic misclassification of LNS as only a small number of lymph nodes, mostly from the hilar regions, were sampled during macroscopic examinations. LNS in unsampled nodes would have been missed. This diagnostic misclassification is probably limited by the purposeful selection of firm lymph nodes suggestive of silicosis by pathologists. This might explain some of the false-negative and true-negative diagnoses. The true extent of misclassification, if any, is unknown.
Predictive values and the summary diagnostic accuracy measures are affected by the prevalence of disease in the population of interest and decrease as prevalence decreases [25]. The measures are, therefore, only generalisable to populations with similar silicosis prevalences.
Although routine RCS monitoring is conducted in mines, the data are not captured in PATHAUT. Hence, we used gold-mining employment duration as a proxy for cumulative RCS exposure, which is a better determinant of silicosis [33]. For example, the same prevalence of PS and LNS was found in the second, third and fourth quartiles of duration (years) of uranium mining, whereas prevalence increased steadily with increasing quartiles of cumulative RCS exposure (mg·m−3). Objective measures of cumulative exposure to RCS may produce greater differentiation in diagnostic accuracy across exposure categories than we found.
In conclusion, the low PPVs for PS in our study suggest deficiencies in the diagnostic role of LNS clinically. The detection of LNS should prompt clinicians to take a detailed occupational history and to initiate investigations for PS, using improved chest imaging if indicated. As LNS is a pathological response to RCS, its detection should prompt evaluations of workplaces for RCS exposures and implementation of improved control, if appropriate.
Acknowledgement
The authors acknowledge the decades of work carried out by the staff of the Pathology Division of the NIOH in conducting autopsy examinations of deceased miners and maintaining the PATHAUT database.
Footnotes
Provenance: Submitted article, peer reviewed.
Ethics statement: Ethical approval for the study was obtained from the University of the Witwatersrand, Human Research Ethics Committee (Medical) (clearance certificate number M220564).
Conflict of interest: N. Ndlovu has nothing to disclose. D. Rees and J. Murray have provided expert reports for silicosis claimants in legal matters. D.G. Lakhoo reports support for the present manuscript from NIOH, National Health Laboratory Service, Johannesburg, South Africa, and Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
References
- 1.Rees D, Murray J. Silica. In: Newman Taylor ACP, Blanc P, Pickering A, eds. Parkes’ Occupational Lung Disorders, 4th Edn. Florida, CRC Press, 2017; pp. 187–206. [Google Scholar]
- 2.Nelson G, Girdler-Brown B, Ndlovu N, et al. Three decades of silicosis: disease trends at autopsy in South African gold miners. Environ Health Perspect 2010; 118: 421–426. doi: 10.1289/ehp.0900918 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Adams K, Shah PL, Edmonds L, et al. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax 2009; 64: 757–762. doi: 10.1136/thx.2008.109868 [DOI] [PubMed] [Google Scholar]
- 4.Ariza-Prota M, Perez-Pallares J, Fernandez-Fernandez A, et al. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: safety, feasibility and diagnostic yield – experience in 50 cases. ERJ Open Res 2023; 9: 00448-2022. doi: 10.1183/23120541.00448-2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Velasco-Albendea FJ, Cruz-Rueda JJ, Gil-Belmonte MJ, et al. The contribution of mediastinal transbronchial nodal cryobiopsy to morpho-histological and molecular diagnosis. Diagnostics (Basel) 2023; 13: 3476. doi: 10.3390/diagnostics13223476 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Poletti V, Petrarulo S, Piciucchi S, et al. EBUS-guided cryobiopsy in the diagnosis of thoracic disorders. Pulmonology 2024; 30: 459–465. doi: 10.1016/j.pulmoe.2023.11.008 [DOI] [PubMed] [Google Scholar]
- 7.Shitrit D, Adir Y, Avriel A, et al. EBUS-TBNA is sufficient for successful diagnosis of silicosis with mediastinal lymphadenopathy. Lung 2018; 196: 441–445. doi: 10.1007/s00408-018-0129-3 [DOI] [PubMed] [Google Scholar]
- 8.Thanthitaweewat VLN, Sriprasart T. Silicosis: role of endobronchial ultrasound and transbronchial needle aspiration. Eur Respir J 2020; 56: 3155. doi: 10.1183/13993003.congress-2020.3155 [DOI] [Google Scholar]
- 9.Tung AH, Ngai JC, Ko FW, et al. Diagnosis of silicotuberculosis by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Respirology 2013; 18: 383–384. doi: 10.1111/resp.12020 [DOI] [PubMed] [Google Scholar]
- 10.Ronsmans S, Decoster L, Keirsbilck S, et al. Artificial stone-associated silicosis in Belgium. Occup Environ Med 2019; 76: 133–134. doi: 10.1136/oemed-2018-105436 [DOI] [PubMed] [Google Scholar]
- 11.Carbonari A, Rossini L, Marioni F, et al. Value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of lung and mediastinal lesions. Rev Assoc Med Bras (1992) 2020; 66: 1210–1216. doi: 10.1590/1806-9282.66.9.1210 [DOI] [PubMed] [Google Scholar]
- 12.Tang CL, Zhu Z, Zhong CH, et al. Clinical application of endobronchial ultrasonography-guided transbronchial needle aspiration biopsy-a single center, large sample, real-world study. BMC Pulm Med 2023; 23: 336. doi: 10.1186/s12890-023-02568-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Mohan A, Madan K, Hadda V, et al. Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations. Lung India 2023; 40: 368–400. doi: 10.4103/lungindia.lungindia_510_22 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Ramarmuty HY, Huan NC, Nyanti LE, et al. Early experience of endobronchial ultrasound-guided transbronchial nodal cryobiopsy: a case series from Sabah, Malaysia. Ther Adv Respir Dis 2024; 18: 17534666241231122. doi: 10.1177/17534666241231122 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Begin R, Ostiguy G, Fillion R, et al. Computed tomography scan in the early detection of silicosis. Am Rev Respir Dis 1991; 144: 697–705. doi: 10.1164/ajrccm/144.3_Pt_1.697 [DOI] [PubMed] [Google Scholar]
- 16.Carneiro APS, da Silva LL, Silva F, et al. Volume-based tomography for the diagnosis of incipient silicosis in former gold miners. Occup Environ Med 2022; 79: 427–432. doi: 10.1136/oemed-2021-107922 [DOI] [PubMed] [Google Scholar]
- 17.Hoy RF, Jones C, Newbigin K, et al. Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers. Respirology 2024; 29: 785–794. doi: 10.1111/resp.14755 [DOI] [PubMed] [Google Scholar]
- 18.Cox-Ganser JM, Burchfiel CM, Fekedulegn D, et al. Silicosis in lymph nodes: the canary in the miner? J Occup Environ Med 2009; 51: 164–169. doi: 10.1097/JOM.0b013e31818f6a0f [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Taeger D, Bruning T, Pesch B, et al. Association between lymph node silicosis and lung silicosis in 4,384 German uranium miners with lung cancer. Arch Environ Occup Health 2011; 66: 34–42. doi: 10.1080/19338244.2010.506494 [DOI] [PubMed] [Google Scholar]
- 20.Murray J, Webster I, Reid G, et al. The relation between fibrosis of hilar lymph glands and the development of parenchymal silicosis. Br J Ind Med 1991; 48: 267–269. doi: 10.1136/oem.48.4.267 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Seaton A, Cherrie JW. Quartz exposures and severe silicosis: a role for the hilar nodes. Occup Environ Med 1998; 55: 383–386. doi: 10.1136/oem.55.6.383 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.RSA . Occupational Disease in Mines and Works Act No. 78 of 1973. Government Printer, Pretoria, 1973. [Google Scholar]
- 23.Hessel PA, Goldstein B, Davies JC, et al. Pathological findings in mine workers: I. Description of the PATHAUT database. Am J Ind Med 1987; 12: 71–80. doi: 10.1002/ajim.4700120108 [DOI] [PubMed] [Google Scholar]
- 24.National Institute for Occupational Health . Pathology Division Surveillance Report - Demographic Data and Disease Rates for January to December 2018: National Institute for Occupational Health, 2020. Date last accessed: 1 October 2024. www.nioh.ac.za/wp-content/uploads/2020/10/2018-PATHAUT-REPORT.pdf
- 25.Simundic AM. Measures of diagnostic accuracy: basic definitions. EJIFCC 2009; 19: 203–211. [PMC free article] [PubMed] [Google Scholar]
- 26.Ndlovu N, Nelson G, Vorajee N, et al. 38 years of autopsy findings in South African mine workers. Am J Ind Med 2016; 59: 307–314. doi: 10.1002/ajim.22574 [DOI] [PubMed] [Google Scholar]
- 27.Hnizdo E, Murray J, Sluis-Cremer GK, et al. Correlation between radiological and pathological diagnosis of silicosis: an autopsy population based study. Am J Ind Med 1993; 24: 427–445. doi: 10.1002/ajim.4700240408 [DOI] [PubMed] [Google Scholar]
- 28.Austin EK, James C, Tessier J. Early detection methods for silicosis in Australia and internationally: a review of the literature. Int J Environ Res Public Health 2021; 18: 8123. doi: 10.3390/ijerph18158123 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Nandi SS, Lambe UP, Sarkar K, et al. A rapid point of care CC16 kit for screening of occupational silica dust exposed workers for early detection of silicosis/silico-tuberculosis. Sci Rep 2021; 11: 23485. doi: 10.1038/s41598-021-02392-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Wang Z, Zhang J, Wang T, et al. The value of single biomarkers in the diagnosis of silicosis: a meta-analysis. iScience 2024; 27: 109948. doi: 10.1016/j.isci.2024.109948 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Hnizdo E, Sluis-Cremer GK. Risk of silicosis in a cohort of white South African gold miners. Am J Ind Med 1993; 24: 447–457. doi: 10.1002/ajim.4700240409 [DOI] [PubMed] [Google Scholar]
- 32.Naidoo RN, Robins TG, Murray J, et al. Validation of autopsy data for epidemiologic studies of coal miners. Am J Ind Med 2005; 47: 83–90. doi: 10.1002/ajim.20112 [DOI] [PubMed] [Google Scholar]
- 33.Chen W, Hnizdo E, Chen JQ, et al. Risk of silicosis in cohorts of Chinese tin and tungsten miners, and pottery workers (I): an epidemiological study. Am J Ind Med 2005; 48: 1–9. doi: 10.1002/ajim.20174 [DOI] [PubMed] [Google Scholar]