Risk Identification and Prediction of Coal Workers’ Pneumoconiosis in Kailuan Colliery Group in China: A Historical Cohort Study

Background

Prior to 1970, coal mining technology and prevention measures in China were poor. Mechanized coal mining equipment and advanced protection measures were continuously installed in the mines after 1970. All these improvements may have resulted in a change in the incidence of coal workers’ pneumoconiosis (CWP). Therefore, it is important to identify the characteristics of CWP today and trends for the incidence of CWP in the future.

Methodology/Principal Findings

A total of 17,023 coal workers from the Kailuan Colliery Group were studied. A life-table method was used to calculate the cumulative incidence rate of CWP and predict the number of new CWP patients in the future. The probability of developing CWP was estimated by a multilayer perceptron artificial neural network for each coal worker without CWP. The results showed that the cumulative incidence rates of CWP for tunneling, mining, combining, and helping workers were 31.8%, 27.5%, 24.2%, and 2.6%, respectively, during the same observation period of 40 years. It was estimated that there would be 844 new CWP cases among 16,185 coal workers without CWP within their life expectancy. There would be 273.1, 273.1, 227.6, and 69.9 new CWP patients in the next <10, 10-, 20-, and 30- years respectively in the study cohort within their life expectancy. It was identified that coal workers whose risk probabilities were over 0.2 were at high risk for CWP, and whose risk probabilities were under 0.1 were at low risk.

Conclusion/Significance

The present and future incidence trends of CWP remain high among coal workers. We suggest that coal workers at high risk of CWP undergo a physical examination for pneumoconiosis every year, and the coal workers at low risk of CWP be examined every 5 years.     

Estimates and Predictions of Coal Workers’ Pneumoconiosis Cases among Redeployed Coal Workers of the Fuxin Mining Industry Group in China: A Historical Cohort Study

This research was aimed at estimating possible Coal workers’ pneumoconiosis (CWP) cases as of 2012, and predicting future CWP cases among redeployed coal workers from the Fuxin Mining Industry Group. This study provided the scientific basis for regulations on CWP screening and diagnosis and labor insurance policies for redeployed coal workers of resource-exhausted mines. The study cohort included 19,116 coal workers. The cumulative incidence of CWP was calculated by the life-table method. Possible CWP cases by occupational category were estimated through the average annual incidence rate of CWP and males’ life expectancy. It was estimated that 141 redeployed coal workers might have suffered from CWP as of 2012, and 221 redeployed coal workers could suffer from CWP in the future. It is crucial to establish a set of feasible and affordable regulations on CWP screening and diagnosis as well as labor insurance policies for redeployed coal workers of resource-exhausted coal mines in China.     

Polymorphisms in chemokine and chemokine receptor genes and the development of coal workers' pneumoconiosis

Chemokines and their receptors are key regulators of inflammation and may participate in the lung fibrotic process. Associations of polymorphisms in CCL5 (G-403A) and its receptor CCR5 (Delta32), CCL2 (A-2578G) and CCR2 (V64I), and CX3CR1 V249I and T280M with coal worker's pneumoconiosis (CWP) were investigated in 209 miners examined in 1990, 1994 and 1999. Coal dust exposure was assessed by job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-year change in CT score, and CWP prevalence in 1999. CCR5 Delta32 carriers had significantly higher CT score in 1990 and 1994 (2.15 vs. 1.28, p=0.01; 3.04 vs. 1.80, p=0.04). The CX3CR1 I249 allele was significantly associated with lower 1990 CT score and lower progression in 4-year change in CT score in CCR5 Delta32 carriers only (p for interaction=0.03 and 0.02). CX3CR1 V249I was associated with lower 1999 CWP prevalence (16.7%, 13.2%, 0.0% for VV, VI and II); the effect was most evident in miners with high dust exposure (31.6%, 21.7%, 0.0%). Our findings indicate that chemokine receptors CCR5 and CX3CR1 may be involved in the development of pneumoconiosis.     

The presence of promatrix metalloproteinase-3 and its relation with different categories of coal workers' pneumoconiosis

Extracellular matrix formation (ECM) and remodeling are critical events related to the pathogenesis of pulmonary fibrosis. Matrix metalloproteinases play an essential role in degrading and remodeling the ECM. In this study, we tried to show the presence and correlation of promatrix metalloproteinase-3 (proMMP-3) (the inactive form of metalloproteinase-3) levels in coal workers' pneumoconiosis (CWP) with different categories. The study population consisted of 44 coal miners with CWP (pos CWP). Coal miners without CWP (neg CWP, n = 24) and non-underground personnel (controls, n = 17) were taken as controls. All coal miners were stable and had no systemic infection or disease. Standard posterio-anterior chest radiographs and pulmonary function tests were performed to exclude any diseases other than CWP. Serum proMMP-3 was analysed using the sandwich enzyme-linked immunosorbent assay according to the manufacturer's instructions (The Binding Site, Birmingham, UK). Mean proMMP-3 values of the all three groups were compared and a significant statistical difference obtained (p < 0.001). In addition, a statistically significant difference was found between categories of the disease and proMMP-3 values (p < 0.05). The effects of age, exposure duration and cigarette smoking on proMMP-3 values in coal miners with CWP were investigated. There were no correlations between age, smoking and proMMP-3 values. However, a positive correlation was found between exposure duration and proMMP-3 values (r = 0.447, p = 0.008). In conclusion, proMMP-3 (prostromelysin 1) may play an essential role in degrading and remodeling the ECM in workers with pneumoconiosis. ProMMP-3 may also reflect the stage of pneumoconiosis disease.     

Chemical reactivity of the carbon-centered free radicals and ferrous iron in coals: Role of bioavailable Fe2+ in coal workers' pneumoconiosis

Striking differences in the prevalence of coal workers' pneumoconiosis (CWP) exist between different coal mine regions. The major factors responsible for the observed regional differences in CWP have not yet been identified. In the present study, chemical reactivity of the carbon-centered free radicals in coals and lung tissues, as well as ferrous iron in the coals, were studied by ESR techniques. The ESR spectra clearly demonstrated the presence of at least two types of carbon-centered free radical species, which might respectively attribute to the macromolecular phase and the molecular phase of coal. Grinding produced free radicals in coals. Exposure of freshly ground coal to air for 28 h induced a slight increase of free radicals for most of the coals, and a slight decrease after 4 months' exposure. The lung tissue samples of coal workers deceased of CWP showed similar ESR spectra as coal samples, and these radicals were highly stable in the lung. After incubation of coals with glutathione, hydrogen peroxide, sodium formate or oxygen, the coal sample from the Gardanne mine which has never induced CWP, and thus is the least hazardous coal, showed the most significant change in the carbon-centered free radical concentration. No significant changes were observed among other coals reported to induce CWP. On the other hand, we found that the coals released different amounts of Fe²⁺ in an acidic medium. Interestingly, the prevalence of CWP correlates positively with the released Fe²⁺ content in these coals and with the amount of oxygen radicals produced by the interaction of Fe²⁺ with O₂ in the acidified coal filtrates. Our studies indicate that the carbon-centered free radicals may not be biologically relevant to coal dust-induced pneumoconiosis, whereas the acid soluble Fe²⁺, which may be dissolved in the phagolysosomes of macrophages, can then lead to Fe²⁺-induced oxidative stress and eventual CWP development.     

Chemical reactivity of the carbon-centered free radicals and ferrous iron in coals: Role of bioavailable Fe2+ in coal workers' pneumoconiosis

Striking differences in the prevalence of coal workers' pneumoconiosis (CWP) exist between different coal mine regions. The major factors responsible for the observed regional differences in CWP have not yet been identified. In the present study, chemical reactivity of the carbon-centered free radicals in coals and lung tissues, as well as ferrous iron in the coals, were studied by ESR techniques. The ESR spectra clearly demonstrated the presence of at least two types of carbon-centered free radical species, which might respectively attribute to the macromolecular phase and the molecular phase of coal. Grinding produced free radicals in coals. Exposure of freshly ground coal to air for 28 h induced a slight increase of free radicals for most of the coals, and a slight decrease after 4 months' exposure. The lung tissue samples of coal workers deceased of CWP showed similar ESR spectra as coal samples, and these radicals were highly stable in the lung. After incubation of coals with glutathione, hydrogen peroxide, sodium formate or oxygen, the coal sample from the Gardanne mine which has never induced CWP, and thus is the least hazardous coal, showed the most significant change in the carbon-centered free radical concentration. No significant changes were observed among other coals reported to induce CWP. On the other hand, we found that the coals released different amounts of Fe²⁺ in an acidic medium. Interestingly, the prevalence of CWP correlates positively with the released Fe²⁺ content in these coals and with the amount of oxygen radicals produced by the interaction of Fe²⁺ with O₂ in the acidified coal filtrates. Our studies indicate that the carbon-centered free radicals may not be biologically relevant to coal dust-induced pneumoconiosis, whereas the acid soluble Fe²⁺, which may be dissolved in the phagolysosomes of macrophages, can then lead to Fe²⁺-induced oxidative stress and eventual CWP development.     

Tumor necrosis factor-alpha gene promoter polymorphism in coal workers' pneumoconiosis

Tumor necrosis factor-alpha (TNF-alpha) is believed to play a central role in the pathogenesis of pneumoconiosis. TNF2, a polymorphism in the TNF-a gene promoter, has been associated with an increase in TNF-alpha production and airway inflammation. To investigate the frequency of TNF2 in patients who have coal workers' pneumoconiosis (CWP) and to determine whether it is associated with development of a large opacity in CWP, we investigated the expression ofthe TNF2 allele in 80 patients who had CWP and in 54 healthy controls using restriction fragment length polymorphism (RFLP). Compared to controls (10.2%), the frequency of the TNF2 allele was greater in the CWP patients (20.6%). Furthermore, the TNF2 allele was very common in patients who had a large opacity (28.2%) in comparison with 13.4% in those with simpleCWP. From these data, we suggest that the TNF2 allele is associated with the development of a large opacity in CWP.     

Circulating Antinuclear Antibody and Rheumatoid Factor in Coal Pneumoconiosis

Circulating antinuclear antibody and rheumatoid factor have been measured in 109 coal miners with pneumoconiosis whose chest radiograph showed a range of abnormalities varying from simple pneumoconiosis of mild degree to advanced progressive massive fibrosis.At a screening dilution of 1/10 the overall incidence of antinuclear antibody was 17%. In almost half of the positive cases the titre was 1/40 or greater.The prevalence of antinuclear antibody was lowest in those with simple pneumoconiosis (9%) and highest in those with category C progressive massive fibrosis (27%). A similar but less striking trend was seen with rheumatoid factor, ranging from 6% in simple pneumoconiosis to 18% in category C progressive massive fibrosis. The trend of increasing frequency of autoantibodies with advancing radiographic category was most marked when the frequencies of antinuclear antibody and rheumatoid factor were combined. These autoantibodies were found in 13% of the miners with simple pneumoconiosis and 45% of those with category C progressive massive fibrosis (P for the trend=0·01).     

煤尘对小鼠肺组织铜蓝蛋白和SOD活性的影响

目的通过接触煤尘后小鼠肺组织中铜蓝蛋白和SOD活性的改变情况,探讨铜蓝蛋白和SOD活性在煤尘肺发展中的意义。方法将50只小鼠随机分成空白对照组、实验对照组和1 h2、h3、h剂量组,采用动式呼吸道染毒,连续染毒12 d,染毒结束后将小鼠处死,测定其肺组织铜蓝蛋白和SOD的活性。结果小鼠脏器系数各组之间无差异;与对照组相比,各剂量组小鼠肺组织SOD活性均降低,差异显著（P〈0.05）,且空白对照与实验对照无差异（P〈0.05）;铜蓝蛋白各组之间无差异。结论短期接触一定浓度煤尘会引起SOD活性的改变。     

Retracted: TNF-α–TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis

Objective : Exposure to coal dust causes the development of coal worker's pneumoconiosis (CWP), which is associated with accumulating macrophages in the lower respiratory tract. This study was performed to investigate the effect of tumor necrosis factor-α (TNF-α)–tumor necrosis factor receptor (TNFR) signal pathway on autophagy and apoptosis of alveolar macrophages (AMs) in CWP. Methods: AMs from controls exposed to coal dust and CWP patients were collected, in which expressions of TNF-α and TNFR1 were determined. Autophagy was observed by transmission electron microscopy, and apoptosis by light microscope and using terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. AMs in CWP patients were treated with TNF-α or anti-TNF-α antibody. Besides, expressions of autophagy marker proteins, apoptosis-related factors, FAS, caspase-8, and receptor-interacting serine–threonine-protein kinase 3 (RIPK3) were determined by western Blot. Activities of caspase-3 and caspase-8 were determined by a fluorescence kit. Flow cytometry was applied to measure the expression of TNFR1 on the surface of the AM. Results: TNF-α expression and TNFR1 expression on the surface of AM, as well as autophagy and apoptotic index were significantly increased in AMs of CWP patients. In response to the treatment of TNF-α, TNF-α expression and TNFR1 expression on the surface of AM as well as LC3I expression were increased, autophagy was decreased, and LC3, LC3II, Beclin1 and B-cell lymphoma 2 expressions decreased, whereas FAS expression and activity and expression of caspase-3 and caspase-8 increased, and apoptotic index increased. Moreover, the situations were reversed with the treatment of anti-TNF-α antibody. Conclusion: TNF-α–TNFR signal pathway was involved in the occurrence and development of CWP by activating FAS–caspase-8 and thus inhibiting autophagy while promoting apoptosis of AM.     

Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population

Background

Coal workers'' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.

Methods

We performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.

Results

The NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.07–1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR = 1.67, 95%CI = 1.15–2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.

Conclusions

This is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings.     

MUC5B promoter polymorphisms and risk of coal workers’ pneumoconiosis in a Chinese population

Coal workers’ pneumoconiosis (CWP) is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Genetic variations have been recognized to be involved in the multi-factorial susceptibility to CWP, and MUC5B is a candidate lung fibrosis susceptibility gene. In the present study, we investigated possible genetic associations between three single nucleotide polymorphisms in MUC5B promoter region and CWP in a case–control study including 686 CWP patients and 680 controls. Genotyping was carried out by TaqMan method. Only rs2672794 allele and genotype frequencies distributions were significantly different between CWP patients and controls (P = 0.017 and 0.046 for allele and genotype, respectively). The MUC5B rs2672794 CC genotype was associated with a significantly increased risk of CWP, compared with the TT genotype. Moreover, individuals with TC/CC genotype had an obviously increased risk of CWP than those with TT genotype, particularly among subgroups of dust exposure <27 years and smokers. This is the first report showing an association between the MUC5B rs2672794 polymorphism and CWP, and our results suggest that MUC5B rs2672794 CC genotype could increase the risk of CWP. Further studies are warranted to confirm our findings.     

Tumor necrosis factor-α gene promoter polymorphism in coal worker' pneumoconiosis

Tumor necrosis factor-alpha (TNF-) is believed to play a central role in the pathogenesis of pneumoconiosis. TNF2, a polymorphism in the TNF- gene promoter, has been associated with an increase in TNF- production and airway inflammation. To investigate the frequency of TNF2 in patients who have coal workers' pneumoconiosis (CWP) and to determine whether it is associated with development of a large opacity in CWP, we investigated the expression of the TNF2 allele in 80 patients who had CWP and in 54 healthy controls using restriction fragment length polymorphism (RFLP). Compared to controls (10.2%), the frequency of the TNF2 allele was greater in the CWP patients (20.6%). Furthermore, the TNF2 allele was very common in patients who had a large opacity (28.2%) in comparison with 13.4% in those with simple CWP. From these data, we suggest that the TNF2 allele is associated with the development of a large opacity in CWP.     

Roles of bioavailable iron and calcium in coal dust-induced oxidative stress: possible implications in coal workers' lung disease

Marked regional differences in prevalence of pneumoconiosis are apparent in the US despite comparable dust exposure. In the present study, we examined the ability of 28 coal samples to release bioavailable iron (BAI) and calcium, as well as other metals such as Cr, Ni, Cu, and Co, from three coalmine regions in Utah (UT), West Virginia (WV), and Pennsylvania (PA), respectively. BAI is defined as iron (both Fe 2+ and Fe 3+ ) released by the coals in 10 mM phosphate solution, pH 4.5, which mimics conditions of the phagolysosomes in cells. We found that coals from the UT, WV, and PA regions released average levels of BAI of 9.6, 4658.8, and 12149 parts per million (ppm, w/w), respectively, which correlated well with the prevalence of pneumoconiosis from that region (correlation coefficient r =0.92 ). The low levels of BAI in the UT coals were due to the presence of calcite (CaCO 3 ), which was shown to be preferentially acid solubilized before iron compounds. Release of iron by two coal samples from the PA and UT regions was further examined in vitro in human lung epithelial A549 cells. We found that the coal from PA, with a high prevalence of pneumoconiosis, released BAI in a dose-dependent manner, both in tissue culture media and in A549 cells. At 2 μg/cm 2 , levels of lipid peroxidation induced by the PA coal were increased 112% over control cells at 24 h treatment, and were sustained at this level for 3 days. The coal from UT, with a low prevalence of pneumoconiosis, induced a marginal increase in cellular iron at 5 and 10 μg/cm 2 treatments and had no effect on lipid peroxidation. Calcium levels in the cells treated with the PA and UT coals were 8.6 and 11.5 μmoles/10 6 cells, respectively, and were significantly higher than that in the controls (53 μmoles/10 6 cells). Our results suggest that the differences in the BAI content in the coals may be responsible for the observed regional differences in the prevalence of pneumoconiosis. Therefore, BAI may be a useful characteristic of coal for predicting coal's toxicity.     

Regression with bivariate grouped data

The problem of accounting for the grouping of continuous, bivariate data in regression analyses is considered. Reasons why grouping must be taken seriously are advanced, and a strategy for accounting for grouping is demonstrated. The specific model asserts that, in the absence of grouping, the data would be bivariate normal. This model is used to adjust estimates of parameters in a regression relating disease severity to a grouped exposure variable, using data on pneumoconiosis in English coal miners (Ashford, 1959, Biometrics 15, 573-581). The choice of computing methods is discussed and likelihood formulas are presented.     

Pulmonary inflammation and crystalline silica in respirable coal mine dust: Dose response

This study describes the quantitative relationships between early pulmonary responses and the estimated lung-burden or cumulative exposure of respirable-quartz or coal mine dust. Data from a previous bronchoalveolar lavage (BAL) study in coal miners (n = 20) and nonminers (n = 16) were used including cell counts of alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs), and the antioxidant superoxide dismutase (SOD) levels. Miners' individual working lifetime particulate exposures were estimated from work histories and mine air sampling data, and quartz lung-burdens were estimated using a lung dosimetry model. Results show that quartz, as either cumulative exposure or estimated lung-burden, was a highly statistically significant predictor of PMN response (P < 0.0001); however cumulative coal dust exposure did not significantly add to the prediction of PMNs (P = 0.2) above that predicted by cumulative quartz exposure (P < 0.0001). Despite the small study size, radiographic category was also significantly related to increasing levels of both PMNs and quartz lung burden (P-values < 0.04). SOD in BAL fluid rose linearly with quartz lung burden (P < 0.01), but AM count in BAL fluid did not (P > 0.4). This study demonstrates dose-response relationships between respirable crystalline silica in coal mine dust and pulmonary inflammation, antioxidant production, and radiographic small opacities.     

An Assessment of the Potential for Selenium to Impair Reproduction in Bull Trout, Salvelinus confluentus, from an Area of Active Coal Mining

Selenium (Se) is an essential nutrient, but in higher concentrations can reduce recruitment in fish populations by increasing rates of deformities during early development. Recent work has identified elevated levels of Se in water and biota collected downstream from coal mining activity in Alberta's northeast slopes region. We also recently identified increased incidence of terata and edema in rainbow trout and brook trout with elevated tissue Se from this area. However, there is currently no information regarding the potential for Se to contribute to declining stocks of bull trout, a species of concern in the area. The present study provides an assessment of the potential for Se to contribute to low recruitment in bull trout downstream from coal mining activity. Non-destructive muscle biopsy sampling and a sensitive atomic fluorescence analysis technique are used to determine Se. Results indicate that most bull trout (>90%) captured immediately downstream from coal mining activity in the region have concentrations of Se that would be expected to impair recruitment. Additional work is required to determine the extent of Se's contribution to low recruitment in bull trout.     

Characterization of alveolar macrophage eicosanoid production in a non-human primate model of mineral dust exposure

The relative activation of eicosanoid production which results from the exposure of the alveolar macrophage (AM) to mineral dusts is thought to be a key factor in the pathophysiology of occupational lung disease. We compared in vitro basal and silica-stimulated production of prostaglandin E₂ (PGE₂) and thromboxane A₂ (TXA₂) by AM from normal humans and non-human primates (Macaca nemistrina). In addition, we instilled mineral dusts directly into one lung of the non-human primate and evaluated AM eicosanoid production at two week intervals following dust instillation. Unstimulated AM from humans produce more PGE₂ and TXA₂ than do AM from M. nemistrina. However, in vitro exposure of AM from both species to silica dust produced a qualitatively similar increase in TXA₂ production accompanied by no change in PGE₂ production. Sequential analysis of AM eicosanoid production following a single bolus exposure to bituminous or anthracite coal dusts, titanium dioxide (TiO₂) dust or crystalline silica showed marked variability among individual non-human primates in qualitative and quantitative aspects of dust-induced eicosanoid production. However, the rank order of potency of the different dusts (silica > anthracite > bituminous) correlated with epidemiological evidence relating the type of dust mined to the incidence of pneumoconiosis. These studies suggest that the non-human primate may serve as a model for the study of both the role of eicosanoids in the etiology of dust-induced occupational lung disease and the biochemical basis for individual variability in the response of lung cells to mineral dust exposure.     

Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers' pneumoconiosis in China: a case-control study

Background

The IL-4, IL-4 receptor (IL4R), and IL-13 genes are crucial immune factors and may influence the course of various diseases. In the present study, we investigated the association between the potential functional polymorphisms in IL-4, IL-4R, and IL-13 and coal workers'' pneumoconiosis (CWP) risk in a Chinese population.

Methods

Six polymorphisms (C-590T in IL-4, Ile50Val, Ser478Pro, and Gln551Arg in IL-4R, C-1055T and Arg130Gln in IL-13) were genotyped and analyzed in a case-control study of 556 CWP and 541 control subjects.

Results

Our results revealed that the IL-4 CT/CC genotypes were associated with a significantly decreased risk of CWP (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.58–0.95), compared with the TT genotype, particularly among subgroups of age <65 years (OR = 0.68, 95%CI = 0.46–0.99) and dust exposure years ≥26 years (OR = 0.69, 95%CI = 0.50–0.94). Moreover, the polymorphism was significantly associated with risk of CWP patients with stage I. In addition, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P _trend = 0.023), and individuals with 11–12 risk alleles had a 47% higher risk of CWP than those with 0–8 risk alleles (OR = 1.47, 95% CI = 1.05–2.05).

Conclusions

Our results suggest that the IL-4 C-590T polymorphism is involved in the etiology of CWP and susceptibility to this disease. Larger studies are warranted to validate our findings.