1. Introduction
Coal workers’ pneumoconiosis (CWP) is a non-neoplastic reaction of the lungs to inhaled mineral or organic dust that does not include asthma, bronchitis, or emphysema. Coal workers’ pneumoconiosis (CWP) is a pulmonary reaction to inhaled coal dust that can take both simple and complicated forms. Many people with CWP are asymptomatic. However, by the time the disease manifests clinically, the lung has suffered extensive irreparable damage. Even if the patient is no longer exposed to coal dust, respiratory disability progresses. Patients have functional deficits in the lungs, including obstructive defects, abnormal diffusing capacities, and restrictive defects. Coal dust exposure causes a variety of co-morbid pulmonary diseases including chronic obstructive pulmonary disease (COPD) [
1,
2,
3]. Decreased pulmonary function in CWP patients contributes to increased premature mortality [
4,
5,
6,
7]. Age-adjusted CWP death rates in the United States have been declining since the 1960s, but an increasing trend in the years of potential life lost (YPLL) before the age of 65 has been observed since 2002 [
4]. The continued occurrence of CWP-attributable YPLL emphasizes the importance of properly assessing CWP severity and progression risk. The findings of a prospective cohort study of coal miners in the United States confirmed that exposure to coal mine dust increases mortality, with pneumoconiosis having the highest standardized mortality ratio [
8]. Patients with CWP frequently displayed respiratory symptoms and a decline in lung function. It has been demonstrated that CWP increases the chance of developing chronic obstructive pulmonary diseases including emphysema and chronic bronchitis [
1,
9,
10]. Chest radiographs are frequently used for pulmonary complication screening or evaluation. However, there are some restrictions on the sensitivity and specificity of imaging workups that begin with simple chest radiographs [
11]. The International Labour Office (ILO) categorization did not correlate with the forced expiratory volume in one second (FEV1) or dyspnea in a cross-sectional investigation [
12]. High-resolution computed tomography scans showed the strongest association between the severity of the impairment and the emphysema score. Since irreversible lung fibrosis appears to be fed by ongoing inflammation, it was proposed that the measurement of coal-dust-induced inflammatory cytokines could be used as a marker of CWP for the identification of high- and low-risk groups [
13]. In therapeutic contexts, however, it is not always easy to get there. Therefore, it could be helpful to have a variety of tools for evaluating respiratory dysfunction and prognosis.
Airway evaluation, including bronchoalveolar lavage (BAL) and bronchial washing, is performed in many CWP patients for various purposes. It is used (1) to find putative mineral dust [
14], (2) to assess other causes of lung disease such pneumonia, sarcoidosis, allergic alveolitis, or lung cancer, and occasionally (3) to reduce the mineral dust burden [
15]. Numerous past studies have shown that BAL is a simple, safe method for determining whether the lower respiratory tract is inflamed. It has been shown that the type of inflammatory response and the severity of the alveolar structure in interstitial lung illnesses are both reflected by an elevated percentage of lymphocytes and neutrophils in BAL fluid, which is frequently referred to as “alveolitis” [
16,
17]. Interstitial pulmonary fibrosis patients are at a higher risk of deterioration when they have a higher neutrophil count [
18]. Occupational lung diseases have drawn attention to BAL fluid as well. Previous research on coal miners has demonstrated that the BAL fluid contains elevated levels of alveolar macrophages, which release excessive reactive oxygen species, several cytokines, and surfactant proteins [
19,
20]. Unlike other interstitial lung diseases, the usefulness of BAL in relation to disease progression and prognosis remains unclear in CWP. By washing the bronchi, it is possible to sample inflammatory cells, caustic organisms, and bronchial epithelial cells in the event of an infection. Certain bronchial epithelial cell characteristics, including squamous metaplasia, hyperplastic epithelial change, and goblet cell hyperplasia, reflect the outcomes of abnormal airway repairs from acute and chronic injuries. However, the clinical ramifications of the continued discovery of these changes in the bronchial epithelial cell in pneumoconiosis patients need to be explored. We postulated that a long-standing inflammatory status of the distal air spaces that is objectively reflected by BAL fluid and proximal air spaces by bronchial cytology and airway cytology from CWP patients shares similar features to those found in chronic obstructive pulmonary diseases. Additionally, in order to address the role of airway cytology in pulmonary mortality, we looked into whether the characteristics of bronchial airway cytology obtained from CWP, when compared with radiologic and functional parameters, have predictive value for the prognosis and short-term survival in cancer-free CWP patients.
4. Discussion
Although it has been suggested that the cellular alterations in BAL fluid serve as a mirror of lung inflammation in a variety of pneumoconiosis [
30,
31,
32], their clinical utility has yet to be determined. We found that examining the differential cell count in BAL fluid was useful for predicting the prognosis in CWP patients, as well as representing the current inflammatory status. Significantly high BAL neutrophils and/or eosinophils, which defined severe alveolitis, were critical. Previous BAL study data for CWP are contentious. Rom and colleagues discovered that alveolar macrophages dominated the inflammatory cells in nonsmokers with complicated CWP [
33]. Although neutrophils made up a very small portion of the total population of inflammatory cells, their proportions were higher in pneumoconiosis (mean value 3.3%). Previously, coal miners without CWP had a higher neutrophil count (mean value 3.7%) than miners with CWP. On the other hand, CWP had a significantly lower lymphocyte count [
20]. The proportion of lymphocytes was reduced in a diverse group of patients exposed to inorganic or organic dust. Regardless of the presence of pneumoconiosis, the cellular profiles of miners revealed a significant decrease in lymphocytes [
30]. The researchers investigated the utility of BAL cellular profiles for monitoring disease progression and the response to treatments for specific interstitial lung diseases. The degree of increase in BAL neutrophils has been linked to disease activity and prognosis in both idiopathic pulmonary fibrosis [
34,
35,
36] and hypersensitivity pneumonitis [
37,
38]. Increases in the eosinophil proportions and numbers were seen in many of the asbestos-exposed individuals [
38] and BAL eosinophilia has been correlated with worse prognosis in idiopathic pulmonary fibrosis [
39]. The eosinophil proportion did not have a significant difference in the pneumoconiosis group in Turkish miners [
30]. In our study, moderate alveolitis was more common in the control group, but when the alveolitis was severe enough, it was significantly higher in CWP patients. Severe alveolitis was also linked to long-term coal dust exposure and massive pulmonary fibrosis. In clinical terms, it is possible that the severity of alveolitis is more important than the mean value of inflammatory cells. The precise roles of eosinophils and neutrophils require further investigation.
Goblet cells that produce mucus are typically found in the spaces between ciliated columnar bronchial cells. These cells frequently multiply to form a bronchial mucosa with goblet cell hyperplasia in the presence of environmental toxins, chronic inflammation, or irritation, as seen in patients with asthma, chronic bronchitis, or bronchiectasis. In our study, CWP patients had a higher prevalence of severe goblet cell hyperplasia than the control group, as would be expected. Additionally, there was a statistically significant correlation between severe goblet cell hyperplasia and fibrosis and declining lung function. This information backs up our initial theory that COPD and CWP share similar respiratory cytologic characteristics. Additionally, this supports the data from earlier studies on COPD in coal miners [
1,
40,
41,
42]. Goblet cell hyperplasia’s function and significance in CWP, however, are not yet well understood. Mucous cell metaplasia results in mucin overproduction, a major condition that contributes to airway obstruction in many chronic airway diseases, including COPD, asthma, and cystic fibrosis [
43]. A variety of factors such as glycoprotein [
44] as proteases secreted by inflammatory cells [
45,
46,
47] are known to induce mucus hyper-production. Goblet cell hypertrophy and hyperplasia have been observed in the airway epithelium of cigarette smokers [
48]. Furthermore, smokers with airflow obstruction have the highest levels of mucin in the epithelium. Notably, in vitro respiratory epithelial cells, tumor necrosis factor (TNF)-
, and interleukin (IL)-1 can induce glycoprotein secretion via ER and MAP kinase signaling [
49]. A similar change has also been observed in alveolar macrophages from coal miners with CWP [
50,
51]. The severity of CWP was found to be directly related to the magnitude of these critical proinflammatory and fibrogenic cytokine releases [
33,
52]. TNF-
is a protein that is released by alveolar macrophages after they ingest dust particles and is linked to the initiation of fibroblast proliferation and collagen deposition [
53]. Based on these findings and the current study, it is possible to hypothesize that similar cytokine pathways involving TNF-
and IL-1 cause goblet cell hyperplasia in CWP. More research is needed to determine the precise role of cytokines in goblet cell hyperplasia and their relationship to pneumoconiosis progression.
This study is novel in that we used two combined airway cytology parameters, alveolitis and goblet cell hyperplasia, to create a pathologic grading system. Aside from the duration of dust exposure, the parameters that were strongly correlated with cancer-free CWP patients were severe alveolitis and goblet cell hyperplasia. After an 80-month follow-up from the initial bronchoscopic cytology examination, Grade 3 patients had a survival rate of 0.2, which was significantly lower than the rate for Grade 2 patients. It implies that patients with CWP who have severe alveolitis and goblet cell hyperplasia are at high risk of pulmonary morbidity. Therefore, we propose that a different follow-up period and therapeutic approach should be taken with patients who have severe alveolitis and goblet cell hyperplasia and ideally with individuals who have either severe alveolitis or goblet cell hyperplasia in their bronchial washing cytology.
However, our study has several limitations. Because this is a retrospective study, the patient populations and follow-up times differed. Furthermore, we were unable to exclude patients who had a suspected infection at the time of the bronchoscopy. Bias due to patient exclusion is also likely to have influenced the study’s findings.