Chest pain in asbestos and silica-exposed workers

Occupational Medicine 2011;61:178–183 Advance Access publication on 14 March 2011 doi:10.1093/occmed/kqr011

Chest pain in asbestos and silica-exposed workers E.-K. Park1, P. S. Thomas2, D. Wilson3, H. J. Choi4, A. R. Johnson5 and D. H. Yates6 1

Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, 807-8555, Japan, 2School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia, 3Department of Industrial Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, 807-8555, Japan, 4Department of Biomedical Laboratory Science, Inje University, 607 Obang Dong, Gimhae, 621-749, Korea, 5Department of Respiratory Medicine, Liverpool Hospital, Sydney, NSW, Australia, 6Department of Thoracic Medicine, St Vincent’s Hospital, Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia. Correspondence to: D. H. Yates, Department of Thoracic Medicine, St Vincent’s Hospital, Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia. Tel: 161 2 8382 2330; fax: 161 2 8382 2359; e-mail: [email protected]

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Aims

To investigate chest pain in a cohort of subjects exposed to asbestos and silica dust applying for compensation.

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Methods

Cross-sectional study using a standardized questionnaire. Data collection included: smoking history, Medical Research Council scales of exercise capacity and respiratory symptoms.

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Results

We studied 621 subjects. Six disease groups were categorized: asbestosis (n 5 27), diffuse pleural thickening (DPT) (132), asbestosis and DPT (14), silicosis (26), pleural plaques only (160) and healthy subjects with a history of dust exposure (256). Crude prevalence rates of chest pain were high, with chest pain approximately twice as common in subjects with asbestos-related disorders and silicosis as in healthy subjects, with an overall frequency of 40%. However, when other variables were taken into account in a multivariate analysis the differences between groups disappeared. The factor most significantly related to chest pain was age.

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Conclusions Chest pain is apparently common in subjects with asbestos-related disorders and silicosis, but after adjustment for other variables, no increased prevalence was apparent in subjects with pleural disorders. More sophisticated questionnaires and dedicated imaging are required to elucidate this further. ...................................................................................................................................................................................

Key words

Asbestos; asbestos-related diseases; prevalence; respiratory symptoms; silica.

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Introduction Millions of people are still exposed to asbestos worldwide [1], particularly in developing countries, and the number of deaths from malignant mesothelioma is still rising [2]. Despite the introduction of occupational exposure control measures in most countries over 30 years ago, asbestos-related pleural diseases are still increasing in Australia and the adverse health effects of asbestos are predicted to continue well into the 21st century [3,4]. With the reduction in levels of asbestos exposure, pleural disorders have come to dominate the spectrum of asbestos-related disease. Circumscribed pleural plaques are the commonest manifestation of asbestos exposure and are still frequently seen in clinical practice, although these are often diagnosed coincidentally. The second most frequent asbestos-related disease is still malignant mesothelioma of the pleura, which is increasing in incidence in Australia [4,5]. Other pleural disorders include

asbestos-related pleural effusion, diffuse pleural thickening (DPT), and rounded atelectasis [6,7]. Malignant mesothelioma may present with chest pain and dyspnoea, but chest pain has also been noted in several studies with non-malignant pleural disease [8,9], particularly DPT and pleural plaques [10]. Clinically, this is an important issue and in addition to the chest pain the patient may be additionally anxious about this symptom, given the publicity surrounding asbestos exposure and mesothelioma. Despite the availability of new investigations and surgical techniques for diagnosing malignancy, it is still extremely difficult in most cases to distinguish between the different asbestos-related pleural diseases in clinical practice unless the disease is advanced. The recent American Thoracic Society (ATS) statement on non-malignant disorders related to asbestos states that ‘chronic pleuritic chest pain is rare in patients with asbestos-related disease and that studies describing

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Background Chest pain may be the first symptom of developing respiratory malignancy, particularly in subjects with asbestos exposure, yet little information exists on this topic.

E.-K. PARK ET AL.: CHEST PAIN IN ASBESTOS AND SILICA-EXPOSED WORKERS 179

the frequency of atypical chest pain in asbestos-exposed subjects have not been performed’ [11]. Overall, little attention has been paid to the symptom of chest pain compared with breathlessness and other respiratory symptoms. Most studies evaluating symptoms in subjects occupationally exposed to asbestos do not include a detailed assessment of chest pain as part of their investigations [12]. In the two studies that have investigated this in some detail [9,13], the findings were discrepant. The aim of this study was to assess the prevalence of chest pain in subjects occupationally exposed to dusts. We assessed respiratory symptoms in 615 subjects who had applied for compensation for occupational respiratory disease and were screened for entry into a study into mesothelioma [14]. Subjects with silica as well as asbestos exposure were included because pleural thickening also occurs with this dust [15].

Data were collected at the Workers’ Compensation (Dust Diseases) Board of New South Wales, Sydney, Australia, from February to November 2006. Full details of this study have already been reported [14]. Briefly, asbestos-exposed workers and workers with other dust exposures and respiratory diseases attending the Board for a routine examination as part of an application for compensation, or as follow-up of a diagnosed occupational disease, were invited to participate in the study. The routine examination included a standardized questionnaire, radiology, lung function measurement, and clinical examination by a thoracic physician. The study was approved by the Human Research Ethics Committee of St Vincent’s Hospital, Sydney, Australia. Participants were not compensated for their participation and gave signed informed consent. The study aimed to compare the prevalence of respiratory symptoms (chest pain, cough and dyspnoea) in participants with different lung diseases as well as those with exposure but no disease. Respiratory symptoms and physical examination were recorded using a physician-administered clinical card. Data collected included smoking history, Medical Research Council scales of exercise capacity, chest pain, cough and dyspnoea, past medical history and details of the physical examination. A chest radiograph was mandatory. High-resolution chest computerized tomography scanning was performed if clinically indicated. For study purposes, the presence or absence of asbestos-related or other diseases was classified according to the determination of the Medical Authority that comprised three respiratory physicians with special expertise in occupational lung diseases. Subject characteristics were summarized for the complete sample (Table 1). Three respiratory symptoms, chest pain, dyspnoea and cough, were treated as outcome variables. Group differences in proportions and

Results A total of 621 subjects agreed to participate in the study. Six disease groups were categorized: subjects with asbestosis (n 5 27), DPT (132), asbestosis and DPT (14), silicosis (26), PPs (160), and those apparently healthy but asbestos exposed (256). One subject withdrew from the project and in one, data were missing. Subjects with both silicosis and asbestosis (n 5 1) or silicosis and DPT (n 5 3) were excluded, leaving 615 eligible for analysis. Most were male (n 5 603, 98%) with only 12 females (2%). Demographic details are shown in Table 1. Subjects with disease were significantly older than asymptomatic subjects (P , 0.01), but were no more likely to have smoked. The crude prevalence of respiratory symptoms in healthy subjects was dyspnoea 28%, chest pain 22% and cough 27%. The crude prevalence of dyspnoea, chest pain and cough differed significantly among the study groups (P , 0.01, Table 1). When individual disease categories were compared with healthy subjects, those in all disease categories were significantly more likely to be breathless, to suffer chest pain and to cough (P , 0.001). Subjects with DPT (n 5 132) and asbestosis/DPT (n 5 14) were more likely to suffer these symptoms than subjects with pleural plaques, both together and as individual categories.


Methods

arithmetic means were tested by chi-square and ANOVA tests, respectively. Body mass index (BMI) was divided into three categories based on World Health Organization criteria [16]. Blood pressure was divided into four categories based on the 2003 American Heart Association criteria [17]. Smokers were categorized into ex-, current, and never-smokers; age and smoking pack-years were arbitrarily divided into eight and four categories, respectively, with an attempt to maintain a relatively good distribution of subjects per category. Stepwise logistic regression (both forward and backward) was performed to identify the more important independent variables associated with the three respiratory symptoms. Any variable with a P value of ,0.15 for any of the three symptoms was retained and included in the subsequent logistic regression analyses. The adjusted odds ratios (AORs) and adjusted prevalence rates (APRs) for the symptoms were calculated while controlling for the following covariates retained in the stepwise regression analyses: age, sex, smoking, smoking pack-years, BMI, presence of diabetes mellitus, hypertension, diagnosed silicosis and four types of asbestos-related diagnoses (asbestosis, DPT, pleural plaques and a combination of asbestosis/DPT). The four asbestos-related diagnoses were not retained in the stepwise regression analyses but were forcefully included in the subsequent logistic regression models. Generalized linear regression models (GLM) were used to calculate APRs and test for trend. All statistical analyses were performed using SAS (version 9.1; SAS Institute, Cary, NC, USA).

180 OCCUPATIONAL MEDICINE

Table 1. Characteristics of subjects with PRs of respiratory symptoms by asbestos-related disease category Characteristic

All

Healthya

Asbestosis

Silicosis

DPT

Asbestosis/ DPT

Pleural plaques

256 (42)

27 (4)

26 (4)

132 (22)

14 (2)

160 (26)

,0.001

61.0 [10.5] 248 (97)

73.0 [6.7] 26 (96)

71.1 [6.2] 26 (100)

71.6 [6.9] 129 (98)

72.9 [6.7] 14 (100)

69.3 [8.9] 160 (100)

,0.001 ,0.001

42 11 47 20.9 [18.1] (%) 28 22 27

63 11 26 25.6 [14.4]

58 8 35 22.0 [15.0]

74 5 21 23.6 [18.7]

86 0 14 15.9 [18.0]

55 8 37 24.5 [23.7]

NS

NS

70 33 67

89 46 69

68 42 52

93 50 79

45 38 43

,0.001 ,0.05 ,0.001

NS, non-significant. a

Apparently healthy with a history of asbestos or silica exposure.

b

For significance testing: chi-square tests were performed for proportions and analyses of variance for arithmetic means.

Chest pain was present in 43% of these subjects compared with 38% of subjects with pleural plaques (non-significant) and dyspnoea in 77% of these subjects compared with 45% of those with pleural plaques (P , 0.001); 67% of subjects with asbestosis reported cough, and in subjects with DPT (52%) and asbestosis/DPT (79%) it was significantly more prevalent than in those with pleural plaques alone (43%, P , 0.05). However, these differences became less significant when age, smoking history and sex were included in the multivariate analysis (Table 2). Statistically significant dose-response trends were observed in the PRs of dyspnoea (by age and smoking pack-years). Odds ratios for dyspnoea were significantly increased by increasing age over 50 years. Current-smokers and subjects who smoked .17 pack-years were, respectively, 12 and 25% more likely to suffer dyspnoea than never-smokers; those who smoked 17–24 pack-years were 33% more likely to experience chest pain than never-smokers. Breathlessness was the only symptom statistically significantly elevated by the presence of disease: an increase of almost 3-fold with silicosis and 14 and 22% increased by the presence of DPT and asbestosis/DPT, respectively.

Discussion Our cross-sectional study found a high overall crude prevalence of dyspnoea, chest pain and cough in subjects attending screening for disease linked to occupational dust exposure but after adjustment chest pain was not significantly increased in those with disease. We found chest pain to be commoner in subjects with DPT, asbestosis or silicosis

compared with pleural plaques but these differences diminished once a multivariate analysis taking into account factors such as age and smoking history was performed. Dyspnoea, chest pain and cough were related more to age and smoking habit than to disease category. Dyspnoea and chest pain were the only symptoms significantly linked to asbestos-related disorders. This is not surprising as our subjects were self-selected on the basis of having symptoms since these data come from a compensation registry. Interestingly, the prevalence of chest pain was not significantly higher in subjects with pleural plaques than in asymptomatic subjects with occupational dust exposure. In terms of crude PRs, our findings are very similar to the study of Mukherjee et al. [9], where 556 subjects who had been exposed to asbestos at Wittenoom, Australia, were assessed with plain chest radiography and a selfadministered questionnaire. This study found that 43% of subjects had some chest pain and that chest pain was associated with both benign pleural and diffuse parenchymal disease. Anginal pain, as assessed by the Rose questionnaire, was associated with benign pleural disease and parenchymal disease, while non-anginal pain was associated with parenchymal disease alone. They suggested that radiological evidence of exposure to asbestos was associated with ischaemic heart disease and that there might be a causal relationship. Subsequently there have been some other studies on this topic including large population studies and a small but significant relationship has been consistently found in most [18–20]. We did not use the Rose questionnaire, which was developed for diagnosing anginal pain, and is predictive of major ischaemic cardiac events including death. However, our subjects were examined by a specialist respiratory


Subjects included in 615 (100) final analysis [n (%)] Age (mean [SD]) (years) 66.7 [10.2] Male [n (%)] 603 (98) Smoking status Ex-smoker (%) 55 Current smoker (%) 9 Never-smoker (%) 37 Pack-years (mean [SD]) 22.7 [19.6] Crude prevalence of respiratory symptoms Dyspnoea 47 Chest pain 32 Cough 41

P valueb

Asbestos-related disease category


Table 2. APR (%) and AORs of respiratory symptoms Exposure variablea

Dyspnoea

Cough

APR (%)

AOR (95% CI)

APR (%)

AOR (95% CI)

APR (%)

AOR (95% CI)

31 33 32 32 37 33 29 26 NS

1.00 1.14 1.07 1.07 0.92 0.87 0.96 1.04

21 25 28 46 49 55 64 63 P , 0.01**

1.00 1.49 1.33 1.55 1.60 1.66 1.93 1.76

37 35 39 45 39 42 46 39 NS

1.00 1.53 1.01 0.91 1.04 0.87 0.93 0.97

34

1.00

41

1.00

41

1.00

30 34

1.04 (0.97–1.11) 0.98 (0.84–1.14)

51 41

1.13 (0.95–1.34) 1.12 (1.04–1.19)

41 50

0.96 (0.83–1.12) 1.01 (0.94–1.08)

34

1.00

41

1.00

41

1.00

38 0.98 (0.57–1.71) 47 1.62 (0.82–2.94) 42 0.86 (0.63–1.18) 51 1.13 (0.81–1.58) 22 1.33 (1.05–1.70) 54 1.25 (1.01–1.51) 30 1.08 (0.95–1.22) 58 1.26 (1.09–1.42) NS P , 0.05* subjects with a history of asbestos exposure, except silicosis) 26 1.00 26 1.00

46 42 50 46 NS

0.76 1.13 0.94 1.04

38

1.00

24 32 33 34

1.23 0.96 0.98 0.99

(0.43–3.55) (0.57–1.56) (0.87–1.01) (0.88–1.11)

30 45 33 46

2.38 2.94 1.14 1.22

(0.84–6.80) (1.49–5.80) (1.06–1.22) (1.01–1.49)

53 51 41 58

2.18 0.91 1.01 0.96

34

0.98 (0.97–1.02)

22

1.00 (0.99–1.01)

39

0.99 (0.98–1.02)

(0.27–4.89) (0.59–1.97) (0.74–1.55) (0.71–1.20) (0.69–1.09) (0.80–1.17) (0.81–1.33)

(1.23–2.09) (0.62–2.84) (1.25–2.99) (1.11–1.99) (1.22–1.98) (1.34–2.06) (1.23–2.09)

(0.37–6.36) (0.56–1.80) (0.64–1.30) (0.78–1.39) (0.69–1.09) (0.77–1.13) (0.76–1.24)

(0.43–1.36) (0.80–1.59) (0.75–1.16) (0.91–1.18)

(0.94–2.78) (0.55–1.50) (0.94–1.09) (0.86–1.08)

APR, adjusted prevalence rate; AOR, adjusted odds ratio; DPT, diffuse pleural thickening; NS, non-significant. The models controlled for age, sex, smoking status, packyears of smoking, BMI, presence of diabetes mellitus, hypertension, diagnosed silicosis and four types of asbestos-related diagnoses (asbestosis, DPT, pleural plaques and combination of asbestosis/DPT. a

All exposure variables were included in GLM models, SAS, to calculate the APRs, and in logistic regression models to calculate the APRs.

physician who used similar questions to explore the possibility of their chest pain being due to angina. All chest pain, not just pleuritic pain was included, and its characteristics were elucidated. If it was deemed anginal, it was recorded as such and not as chest pain. Thus, our definition is likely to include pain from a variety of causes including some of cardiac and gastrointestinal origin, which accurately reflects clinical practice but is not specific for pleural pain. However, no questionnaire specific for pain due to chest disease currently exists, although several have been well validated for other respiratory symptoms (e.g. the St George’s Respiratory Questionnaire). In our study, unlike that of Mukherjee et al. [9], the significance of the symptom of chest pain disappeared after adjustment for co-variables, in common with earlier reports [13,21]. Broderick et al. [13] specifically exam-

ined pleural abnormalities in a cohort of sheet metal workers, 334 of whom had pleural disease. They found that chest pain was related to pleural disease but the statistical significance disappeared after adjustment for other factors. Overall, its prevalence was low, as in the study of Jarvholm and Larsson [21]. In the latter subjects with a history of cardiac disease were however excluded. The ATS statement [11] that chronic severe pleuritic pain is rare in patients with asbestos-related disease is substantiated by our results. There are several potential defects in our study, which aimed only to evaluate common respiratory symptoms in our study population. The methodology we used for assessing chest pain was crude but was that used both clinically and in earlier studies. The study subjects were likely to be a selected group as they were attending for


Age (years) ,51 (n 5 47) 51–55 (n 5 45) 56–60 (n 5 70) 61–65 (n 5 100) 66–70 (n 5 103) 71–75 (n 5 113) 76–80 (n 5 107) .81 (n 5 34) P for trend Smoking Never-smokers (n 5 226) Ex-smokers (n 5 339) Current smokers (n 5 54) Pack years Never-smokers (n 5 226) 0–10 (n 5 106) 10–17 (n 5 75) 17–24 (n 5 68) .24 (n 5 144) P for trend Asbestos-related disease (all Apparently healthy (n 5 256) Asbestosis (n 5 27) Silicosis (n 5 26) DPT (n 5 132) Asbestosis/DPT (n 5 14) Pleural plaques (n 5 160)

Chest pain

182 OCCUPATIONAL MEDICINE

Key points • Chest pain may be the first sign of malignancy, particularly in subjects with asbestos exposure, but little information is available on characteristics that may distinguish this from benign pain. • Chest pain was apparently common in subjects with asbestos-related disorders and silicosis, but after adjustment for other variables, no increased prevalence was found compared with control subjects. • This study suggests that more sophisticated questionnaires and dedicated imaging are required to further elucidate factors associated with chest pain after occupational asbestos and silica exposure.

Funding Scientific Committee of the Dust Diseases Board, but otherwise this entity made no intellectual, scientific or other contribution.

Acknowledgements We thank the participants who kindly assisted us with the study and also the Workers’ Compensation Board (Dust Diseases Board) clerical staff.

Conflicts of interest There are no conflicts of interest.

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compensation screening. Most were male, so our results apply only to men and were on a variety of treatments for other diseases. Asbestos exposure varied, as did smoking history. We were unable to adjust for severity of disease using computerized tomography (CT) findings due to the lack of standardization of CT scanning technique, although a CT scoring system has been shown to be helpful in this regard [22]. Nonetheless, our subjects are representative of workers who have been exposed to asbestos and silica in New South Wales, Australia, over the last 40 years. Ideally, future studies should use a specific symptom questionnaire and a less biased cohort of subjects, including those with chest pain unassociated with occupational exposures. Despite our study’s negative findings, they do not exclude the possibility that chest pain in asbestos-related disorders may still be a significant problem for some individuals. Group data, especially when measured using relatively crude methodology, may miss individual differences. It is easy to make errors when using simple clinical methods for assessing pleural disease [23]. Chest pain also occurs in patients who have undergone thoracic surgery (including thoracoscopic procedures) and occasionally after other procedures such as pleural biopsy or pleural chest drainage, e.g. for pneumothorax, or in patients who have residual pleural disease after pneumonia or tuberculosis. This is occasionally sufficiently severe to require referral to a specialist pain service. Evidencebased information regarding chest pain in patients with asbestos-related disorders (and in these other patients) is scanty and should be investigated further using more sophisticated tools. In conclusion, our results suggest that chest pain is common and requires careful examination to exclude factors other than asbestos and silica before attributing it to occupational exposures. A specific questionnaire is needed, as are standardized dedicated imaging techniques. Only with these tools can the cause of chest pain in patients with occupational dust exposures be properly elucidated.


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