Abstract
Background:
Diagnosis of lung diseases associated with silica exposure typically relies on a history of occupational silica dust exposure and chest X-ray. Diffusing capacity of the lung for carbon monoxide (DLCO) is a pulmonary function test that measures the lungs’ ability to transfer gas from inspired air to the bloodstream.
Aims:
To analyses the role of DLCO in the early detection of lung function impairment in asymptomatic or symptomatic workers exposed to silica dust for 5 years or more.
Settings and Design:
An observational study conducted in a tertiary care center of Rajasthan.
Methods and Materials:
A total of 50 silica-exposed workers without a history of Tuberculosis and other pneumoconiosis were enrolled based on inclusion criteria. Each participant underwent a detailed clinical history, physical examination, chest X-ray, hemoglobin, spirometry, and DLCO.
Statistical Analysis Used:
Pearson and Spearman tests were used for correlation. Categorical data were compared by the Chi-square test, and medians were compared with the Mann-Whitney U test. A P value less than 0.05 was considered significant.
Results:
The study population had a median age of 44 years, and 90% were male. The median duration of silica exposure was 15.5 years, and the majority were stone-cutters. DLCO and spirometry detected abnormalities in 72% and 52% of the study population, respectively. Notably, more than half (66.6%) of the participants with normal spirometry had impaired DLCO, recommending the addition of DLCO in the surveillance of silica-exposed workers. A significant correlation was observed between the duration of silica exposure and the severity of impairment.
Conclusions:
DLCO can detect lung function impairment in asymptomatic or mildly symptomatic silica-exposed workers.
Keywords: DLCO, early detection, silica-exposed worker, spirometry
INTRODUCTION
Silica is one of the most common elements on the surface of the Earth, and it is abundantly available.[1] Silica is a major component of rocks, including granite, slate, and sandstone.[2] Silica exists in both crystalline and amorphous forms. Amorphous forms are relatively nontoxic after inhalation.[3] In contrast, inhaled crystalline silica (quartz, cristobalite, and tridymite) is associated with a spectrum of pulmonary diseases.[4]
In India, an estimated 10 million workers are exposed to respirable crystalline silica (RCS) annually, with the problem being particularly severe in the unorganized sector.[5] In Rajasthan, a key mining and mineral processing hub, over 6 million workers are at risk of developing silicosis.[6] Although the cause of silicosis is undisputed, millions of workers worldwide continue to be exposed to hazardous levels of RCS.[7] When inhaled, RCS particles (0.5 to 5 microns in diameter) become embedded in the alveolar sacs, triggering inflammation and scarring. This damage to lung tissue reduces its capacity to facilitate gas exchange and supply oxygen to the blood.[8]
Occupational respiratory diseases often have a long latent period, leading to diagnosis at late stages when therapeutic measures are ineffective.[9] The principal method of diagnosis, as per ILO (International Labor Organization) guidelines, involves a history of occupational exposure and analysis of chest X-rays.[10] Radiological changes often lag behind functional impairment.[11]
Silica-associated lung diseases are preventable with no effective cure; lung transplantation is the only option in near-fatal cases.[12] Given the lack of treatment, effective control of exposure is the cornerstone of prevention.[13] Timely diagnosis and worker education are crucial to prevent disease progression.
Commonly used pulmonary function tests are spirometry and the diffusing capacity of the lung for carbon monoxide (DLCO). While spirometry measures inspiratory and expiratory air volumes to detect ventilatory defects, it may appear normal in the early stages of the disease, as per some studies.[14] DLCO, also known as the transfer factor, measures the lung’s ability to transfer gas to the bloodstream. It is one of the most common and widely used pulmonary function tests after spirometry for the prognostic evaluation of occupational lung disease, like silicosis.[15,16] In addition to that, the DLCO test is convenient and easy to perform.
There is limited literature available that assesses the role of DLCO in the early identification of people developing disease from their silica exposures. The study aims to assess the role of DLCO in early detection of lung function impairment in asymptomatic or symptomatic (mMRC dyspnea grades 0 and 1) workers exposed to silica dust for 5 years or more.
SUBJECTS AND METHODS
This was an observational study among asymptomatic or symptomatic (mMRC dyspnea grades 0 and 1) workers exposed to silica dust for 5 years or more. The sample size was calculated at a 95% confidence interval using the appropriate statistical formula. Workers with active tuberculosis, history of Tuberculosis, workers with other pneumoconiosis (asbestosis, coal workers pneumoconiosis, etc.), and workers with contraindication for spirometry and DLCO were excluded from the study based on clinical and Chest X Ray PA view findings.
The Institutional Ethics Committee approved the study. Subjects were selected consecutively from the silicosis certification clinic in a tertiary care center, Rajasthan, India, and further classified according to their job profile, regardless of their specific industrial sector. Fifty participants constituted the final study population. Participants were informed regarding the objective of the study and written informed consent was obtained from all participants. A structured questionnaire was used to collect detailed data on demographics (age, gender, locality, educational status), occupational history (type of work, daily exposure hours, total exposure years), symptoms, addiction, and pre-existing comorbidities. Hemoglobin, spirometry, and DLCO were performed for all participants.
Spirometry was performed using the Breeze software according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. FEV1/FVC greater than or equal to 70% and FVC greater than or equal to 80% of predictive value is considered normal. FEV1/FVC less than 70% and FVC less than 80% of the predicted value are considered abnormal. In participants with abnormal spirometry, the severity of lung function impairment is graded using FEV1 as per ERS/ATS recommendations.[17,18]
DLCO was measured by the single-breath hold technique (GANSHORN Power Cube Diffusion+, Germany) according to 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. The predicted DLCO was corrected for alterations in hemoglobin concentration as per ERS/ATS recommendations.[19]
Test gas used to calculate DLCO contains 0.3% carbon monoxide, 21% oxygen, a tracer gas (helium), and a balance of nitrogen. The maneuver was demonstrated and explained to each study participant. The participant was seated for at least 5 min before the procedure and remained seated throughout the procedure. The subject breathes quietly while he/she is connected to the instrument. The participant performs a maximum expiration to residual volume, followed by a maximum inspiration of gas mixture to the total lung capacity. Inhalation should be sufficiently rapid such that 85% of the inspired volume (Vi) must be inspired in <4 sec. After the inspiration of this gas mixture, the breath is held for 10 sec, followed by a maximum expiration. During expiration, a volume of gas must be expired to clear the total anatomical and equipment dead-space volume (V.D.) and then discarded before the alveolar sample is collected. After the expired volume is sufficient to clear the volume of the tracheobronchial dead space in that gas exchange does not occur, a gas sample is obtained. Analysis of the C.O. and tracer gas concentrations in the expired gas permits calculation of the diffusing capacity. DLCO (% predicted), carbon monoxide transfer coefficient (KCO) (% predicted), and Alveolar volume-VA (% predicted) were obtained. DLCO (% predicted) 76–140 is considered normal. Impaired DLCO was graded as per ERS/ATS recommendations[18]
Statistical analysis
Continuous data were represented as mean ± SD or median with 25th–75th quartiles. Categorical data was represented by numbers and percentages. Pearson and Spearman tests were used for correlation. Categorical data was compared by the Pearson Chi-square test, and, median was compared with the Mann-Whitney U test. A P value less than 0.05 is considered significant.
RESULTS
The median age of the 50 participants was 44 years (38.75–50.25). The study group consists of predominantly male participants (90%) and resided in rural areas (80%). Twenty (40%) participants were smokers. The median years of silica exposure was 15.5 years (11.5–23.25). The most common occupations were stone cutting (28%) and a combination of stone cutting and drilling (24%). The most frequently reported symptoms were mMRC grade 1 breathlessness (50%) and dry cough (42%). 28% of the participants were asymptomatic [Table 1].
Table 1.
Clinical characteristics of study participants
| Characteristics | Number (%)/Median (25th–75th quartiles) | |
|---|---|---|
| Age | 44 (38.8–50.3) years | |
| Sex | Male | 45 (90%) |
| Female | 5 (10%) | |
| Locality | Rural | 40 (80%) |
| Urban | 10 (20%) | |
| Symptoms | Breathlessness (mMRC 1) | 25 (50%) |
| Dry cough | 21 (42%) | |
| Productive cough | 4 (8%) | |
| Chest pain | 15 (30%) | |
| Asymptomatic | 14 (28%) | |
| History of smoking | 20 (40%) | |
| HYPERTENSION | 18 (36%) | |
| T2DM | 8 (16%) | |
| Type of occupation | Driller | 9 (18%) |
| Grinder | 4 (8%) | |
| Grinder + driller | 4 (8%) | |
| Labourer | 6 (12%) | |
| Stone cutter | 14 (28%) | |
| Stone cutter + driller | 12 (24%) | |
| Stone cutter + driver | 1 (2%) | |
| Duration of exposure to silica | 15.5 (11.5-23.3) years | |
| Present occupational exposure to silica | 31 (62%) | |
mMRC=Modified Medical Research Council, T2DM=Type 2 Diabetes Mellitus
The median spirometry values were: FEV1/FVC: 73.5% (64.25–81); FVC%: 81% (68.50–90.25); and FEV1%: 66.50% (52.75–78.75) [Table 2]. A total of 52% (n = 26) of the participants had abnormal spirometry. Among those with abnormal results, most had moderate (26.9%), or moderate to severe (26.9%) impairment.
Table 2.
DLCO and Spirometry characteristics of the study population
| Parameters | Median (25th–75th percentile) |
|---|---|
| DLCO | |
| DLCO (% Predicted) | 66.5 (53–77) |
| CORRECTED DLCO (% Predicted) | 66.7 (55.3–77.2) |
| KCO (% Predicted) | 93 (75.5–113) |
| VA (% Predicted) | 73.5 (65–85) |
| SPIROMETRY | |
| FEV1/FVC | 73.5 (64.25–81) |
| FVC% | 81 (68.50–90.25) |
| FEV1% | 66.50 (52.75–78.75) |
DLCO=Diffusing Capacity of Lung for Carbon Monoxide, KCO=Carbon Monoxide Transfer Coefficient, VA=Alveolar Volume, FEV1=Forced Expiratory Volume 1, FVC=Forced Vital Capacity
The median DLCO (% Predicted) for the study population was 66.5% (53–77) [Table 2]. A total of 72% (n = 36) of participants were found to have impaired DLCO. Among these, the most common severity was mild impairment (52.8%). The median hemoglobin-corrected DLCO (% Predicted) was 66.7%, which was not significantly different from the uncorrected value (P = 0.284).
Out of the 24 participants with normal spirometry, 66.6% (n = 16) had impaired DLCO.
A significant correlation was observed between the duration of silica exposure and the severity of DLCO impairment (Spearman’s rho = 0.383, P-0.003). In contrast, no significant correlation was found between exposure duration and the severity of spirometry impairment (Spearman’s rho = 0.14, P-0.167); however, a positive trend was noted [Figure 1].
Figure 1.
(a) Correlation between severity of spirometry impairment and median duration of silica exposure, P = 0.167; (b) Correlation between severity of DLCO impairment and median duration of silica exposure, P = 0.003. DLCO = Diffusing Capacity of Lung for Carbon Monoxide
On comparing DLCO with spirometry variables (FEV1/FVC, FVC, FEV1), all the variables showed positive correlation with DLCO. However, a significant correlation is observed in FEV1 (P-0.02), followed by FVC (0.05) [Figure 2]. There is a significant difference between the median duration of exposure in the normal DLCO group, that is, 15 (10–15.25) years, and the impaired DLCO group, that is, 19 (15–25) years, with a P value of 0.020 [Table 3].
Figure 2.
Correlation between % predicted DLCO and spirometry variables. (a) FEV1/FVC vs DLCO, Pearson correlation coefficient-0.08, P-0.298 (b) FVC vs DLCO, Pearson correlation coefficient-0.23, P-0.05 (c) FEV1 vs DLCO, Pearson correlation coefficient-0.28, P-0.02. DLCO = Diffusing Capacity of Lung for Carbon Monoxide, FEV1 = Forced Expiratory Volume 1, FVC = Forced Vital Capacity)
Table 3.
Subgroup analysis comparing the participants of normal DLCO and impaired DLCO
| Characteristics | Normal DLCO (14) | Impaired DLCO (36) | P | |
|---|---|---|---|---|
| Gender | Male | 14 | 31 | 0.142 |
| Age (Median) | 42.5 (31.75–53) | 44 (39–49.75) | 0.494 | |
| Locality | Rural | 11 | 29 | 0.579 |
| Smoking History | Smoker | 7 | 13 | 0.368 |
| Occupational exposure group | Low–dust–producing work | 1 | 5 | 0.455 |
| High–dust–producing work | 13 | 31 | ||
| Duration of silica exposure | 15 (10–15.25) | 19 (15–25) | 0.020 | |
| Present exposure to silica | 10 | 21 | 0.392 | |
| Breathlessness | 8 | 17 | 0.529 | |
| Dry Cough | 7 | 14 | 0.475 | |
| Productive cough | 0 | 4 | 0.193 | |
| Chest pain | 6 | 9 | 0.216 | |
DLCO=Diffusing Capacity of Lung for Carbon Monoxide
DISCUSSION
This study, conducted in a high-risk population in Rajasthan, demonstrates that DLCO can be an important utility for the early detection of lung function impairment in silica-exposed workers.
The demographic profile of our cohort, predominantly males in their 40s residing in rural areas engaged in stone cutting, is consistent with other epidemiological studies from India.[15,20] The median silica exposure duration of 15.5 years highlights the long-term nature of this occupational hazard, which is relatively shorter than the mean exposure periods in many previous studies on silicosis patients (e.g., 18.88 years by Saranya Rajavel et al.,[8] 23.6 years by Law W.Y. et al.,[21] and 22 years by Malmberg et al.)[16]
In this study, the most prevalent symptoms were breathlessness (50%) and dry cough (42%), with chest pain (30%) also commonly reported. Productive cough (8%) was less frequent. This symptom pattern largely aligns with findings from other studies; for instance, Govindagoudar et al.[22] reported breathlessness as the most common symptom (92%), followed by cough (61.9%), and chest pain (48.3%). Keerthivasan Sivanmani et al.[23] also noted a similar trend. However, a key difference in our study was that 28% of our participants were asymptomatic. This discrepancy likely stems from the fact that the other studies primarily involved silicosis patients seeking clinical care due to symptoms, whereas our study included both asymptomatic and mildly symptomatic (mMRC dyspnea grades 0 and 1) workers seeking silicosis certification.
Our spirometry analysis revealed that while median FEV1/FVC ratios (73.5%) and FVC values (81%) of the participants were within the normal range, median FEV1 was notably lower at 66.5%. This observation is consistent with research by Sohrabi et al.[24] and Dixit et al.[25] on silicotic workers, which identified FEV1 as the parameter with the most significant reduction.
DLCO analysis revealed an absolute median DLCO of 6.2 (4.8–7.6) mmol/min/kPa, median DLCO (% predicted) of 66.5% within our study population, indicating impaired gas exchange. Even after correcting for hemoglobin levels, our study found the median corrected DLCO (% predicted) to be 66.7%, with no significant change. This finding may be attributed to the near-normal hemoglobin levels in our participants (median 13.1 g/dl for females and 14.7 g/dl for males), which align closely with the ERS/ATS guideline reference values (13.4 g/dl for females and 14.6 g/dl for males). Median KCO (% Predicted) is 93 (75.50–113) and median VA (% Predicted) is 73.5 (65–85). Further analysis between the normal and impaired DLCO groups revealed a significant variation in KCO and VA. The significant difference in KCO is particularly noteworthy, as it reflects abnormalities in the alveolar-capillary membrane, which is a key site of damage in silicosis.
Interestingly, our study revealed that even among participants with normal spirometry, a significant 66.6% showed impaired DLCO. This suggests that DLCO may be a more sensitive indicator of subtle lung dysfunction than spirometry, especially when airflow limitation has not yet manifested. This finding is consistent with Santosh Kumar et al.’s,[26] a case-control study, which found a statistically significant difference in DLCO (P-0.030) between apparently healthy stone workers and controls, concluding that DLCO reduction is an earlier disease indicator, even when spirometry remains normal in over half of cases. Mohan Bandhu Gupta et al.’s.[27] study on cured pulmonary tuberculosis patients similarly observed reduced DLCO in over half of those with normal spirometry. These results collectively indicate that DLCO abnormalities can precede spirometry changes in certain respiratory conditions, offering crucial implications for earlier diagnosis and intervention to potentially improve patient outcomes.
Our study found a significant positive correlation between the duration of silica exposure and the severity of DLCO impairment (Spearman’s rho = 0.383, P = 0.003). This indicates that longer exposure to silica dust is linked to a greater reduction in the lungs› gas exchange capacity. Interestingly, we observed no significant correlation between silica exposure duration and spirometry-based severity grades (Spearman’s rho = 0.14, P = 0.167), although a positive trend was present. This lack of statistical significance for spirometry might be due to our small study sample and their relatively low median silica exposure.
Our study’s participant breakdown revealed 60% non-smokers, 28% former smokers, and 12% current smokers. Although smoking is a recognized contributor to reduced DLCO, with Francisco Garcia Rio et al.[28] noting higher impairment rates in smokers (26.7%) compared to former (14.4%) and never smokers (6.7%)—we surprisingly observed no significant link between smoking status and DLCO impairment in our study. This finding implies that among individuals with substantial silica exposure, the occupational risk might be the dominant factor affecting DLCO, possibly overshadowing the influence of smoking.
When we compared clinical characteristics between participants with normal DLCO (N = 14) and those with impaired DLCO (N = 36), the duration of silica exposure was the only factor showing a clinically significant difference (P = 0.020). This indicates that longer exposure to silica dust is associated with reduced gas exchange capacity. This finding directly supports our earlier correlation analysis, which established a significant positive relationship between exposure duration and DLCO severity.
Our study is significant for several reasons. First, it is one of the few to investigate the role of DLCO in detecting early lung changes in asymptomatic or symptomatic (mMRC dyspnea grades 0 and 1) workers exposed to silica dust. Second, it explores the utility of DLCO, a modality not commonly used in this context, for our specific study population. In addition to that, it focuses on the population of Rajasthan, where stone-based industries are prevalent, making it a high-risk group. Our limitations include a relatively small sample size, all of whom visited the hospital for silicosis certification purposes, which may not fully represent the broader population. Additionally, further prospective studies may be necessary to validate these findings.
To conclude, DLCO can detect lung function impairment in silica-exposed workers, particularly in asymptomatic or mildly symptomatic conditions, and the severity of impairment is significantly correlated with duration of silica exposure. DLCO test is convenient and the ten seconds of breath holding required for DLCO maneuver is easier for most patients to perform than the forced exhalation required for spirometry. Therefore, DLCO can serve as an effective tool for earlier intervention and potentially improving long-term outcomes in the ongoing battle against occupational lung disease.
Key messages
The study population exhibited below-normal DLCO parameters; the difference in carbon monoxide transfer coefficient (KCO) was more statistically pronounced (P < 0.001).
Duration of silica exposure is strongly correlated with the severity of DLCO impairment.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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