_________________________________
1Chest Clinic C, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN
_________________________________
2North Bristol Lung Centre, Southmead Hospital, University of Bristol, Bristol BS10 5NB
Correspondence to: G P Currie graeme.currie@nhs.net
Cite this as: BMJ 2009;339:b3209
<DOI> 10.1136/bmj.b3209 http://www.bmj.com/content/339/bmj.b3209
People exposed to asbestos often develop lung disease in later life; manifestations include benign, malignant, or diffuse interstitial lung disease. This evidence based review covers who is considered to be at risk, different ways that exposure to asbestos affect the lung, and matters relating to compensation. Because many doctors in primary and secondary care encounter patients who have been exposed to asbestos, they need to be aware of how different people can be affected.
All people who have worked with asbestos are at potential risk of asbestos related lung disease through inhalation of fibres. Asbestos is a mineral silicate that occurs naturally in various forms. It is resistant to heat and other means of destruction, which explains its extensive use during the 19th and 20th centuries. The fibrous nature of asbestos allows it to be woven into cloth or incorporated into cement materials, ceiling tiles, brake and clutch linings, pipe and boiler insulation, flooring, resins, polymers, and filter papers.
Historically, people with the highest exposures worked in asbestos mining, milling, and production of asbestos textiles. Countries that currently produce large amounts of asbestos include Russia, Kazakhstan, China, and Canada. In the 1920s to 1940s asbestosis developed in textile workers with a latency of only a few years and progressed rapidly to death, because exposure was high.1 w1 w2 The risk to people using asbestos products was recognised in shipyard workers in the 1950s, and an association with mesothelioma was determined in the 1960s through a case-control study in South African miners.2 However, one of the first suggestions that exposure to asbestos can cause lung disease was in 1899 in an industrial diseases board of enquiry.3 Today, most people with asbestos related lung disease have a clear history of exposure, such as mixing asbestos cement or fitting insulation (builders), working with asbestos insulation materials (plumbers and electricians), or cutting asbestos cement sheet materials, although some may have been exposed without their knowledge (for example, shipyard workers or ship engineering workers). The lifetime risk of developing mesothelioma was highlighted in a recent study in which joiners, plumbers, electricians, painters, and construction workers had a greater likelihood of being diagnosed within the general population.4 The occurrence of asbestos related lung disease in spouses who laundered the clothing of workers exposed to asbestos is also well established.5 A detailed occupational history—to determine the occupation, what it involved, dates of employment, and length of asbestos exposure—is therefore important in all patients presenting with respiratory symptoms.w3 Because of the unregulated use of asbestos in developing countries, the incidence of asbestos related lung disease worldwide is likely to rise significantly in the years ahead.
SOURCES AND SELECTION CRITERIA
We comprehensively searched articles published up to February 2009 using PubMed and Medline. Key words and phrases used were “asbestos”, “malignant mesothelioma”, “pleural plaques”, “pleural thickening”, “asbestosis”, “lung cancer”, “cigarette smoking”, “pleural effusions”, “compensation”, “occupation”, “chemotherapy”, “radiotherapy”, “surgery”, “treatment”, and “survival”
SUMMARY POINTS
The shape of asbestos fibres results in their retention within the lung. Clearance from the lung occurs by the mucociliary ladder and phagocytic ingestion by macrophages or endocytosis by pneumocytes, but migration to the pleural surface can occur via the lymphatic system.6 The common forms of asbestos exist as serpentine curved fibres (chrysotile (white)) or amphibole straight fibres (crocidolite (blue), amosite (brown), and anthophyllite). Curved fibres carry a slightly lower risk of lung disease than straight fibres,w4 although no safe threshold of exposure to asbestos of any type exists.
Benign pleural disease
Pleural plaques
Pleural plaques consist of layers of hyalinised collagen fibres usually found on the parietal pleura, and they occur in 20-60% of people who have been exposed to asbestos.7 w5 They most commonly appear as calcified areas adjacent to the sixth to ninth ribs and along the surface of the diaphragm, but they tend not to be evident at the lung apices or costophrenic angles. Pleural plaques can usually be identified on a chest radiograph (fig 1), although computed tomography is more sensitive and distinguishes them from solid tumours if the diagnosis is uncertain. They do not undergo malignant change or generally cause symptoms, although pleural plaques have been associated with anginal pain.8
Diffuse pleural thickening
Diffuse thickening of the pleura is less specific to asbestos exposure than pleural plaques. It may occur after exposure to asbestos, but other causes include previous haemothorax, tuberculosis, chest surgery, radiation, infection, and exposure to drugs such as methysergide. Diffuse pleural thickening on a chest radiograph is characterised by a smooth continuous pleural density affecting at least 25% of the lateral chest wall, with or without blunting of the costophrenic angle.w6 It has also been defined on computed tomography as a continuous sheet of pleural thickening (>5 cm wide, >8 cm in craniocaudal extent, and >3 mm thick).9 In extensive diffuse pleural thickening, patients may become breathless and have a restrictive ventilatory defect on lung function tests. In diffuse thickening (which is usually bilateral), the pleura will appear smooth, and the mediastinal border will be unaffected, whereas in mesothelioma, the pleura is likely to be unilaterally irregularly thickened and the mediastinal border affected. If the diagnosis is uncertain, computed tomography and biopsy are warranted.
Fig 1 Chest radiograph showing pleural plaques (A), pleural thickening (B), and calcification of the diaphragm (C)
Benign asbestos related pleural effusion
Benign exudative pleural effusions are often preceded by episodes of “asbestos pleurisy.” They can occur within 15 years of asbestos exposure10 but may also appear much later.w7 Because of confusion with a malignant effusion, a pleural biopsy is usually needed, and this shows non-specific inflammation. Benign effusions may resolve spontaneously (often leaving an area of pleural thickening) or require drainage if large enough to cause symptoms.
Interstitial lung disease
Asbestosis
Asbestosis is caused by inhalation of asbestos fibres and is a typical pneumoconiosis (interstitial lung disease caused by inhaled inorganic dusts). The condition is directly related to the magnitude and duration of exposure to asbestos.11 After a latent period of 20-30 years, patients with developing asbestosis experience an insidious onset of breathlessness and reduced exercise tolerance; cough, sputum production, and wheezing are less common. As the condition progresses, fine bilateral inspiratory crackles, finger clubbing, and cor pulmonale may occur. Data from the Health and Safety Executive indicated that 111 deaths in the United Kingdom in 2006 were caused by asbestosis, and that 393 death certificates mentioned asbestosis (www.hse.gov.uk/statistics/causdis/asbestosis/index.htm).
Pulmonary function tests show reduced gas transfer, reduced lung volumes, a restrictive ventilatory defect, and exercise related hypoxaemia. Chest radiography may be normal,12 but usually shows bilateral lower zone interstitial changes, often with pleural plaques and thickening. High resolution computed tomography is a more sensitive tool (fig 2), and characteristic features include coarse parenchymal bands, subpleural linear densities, interstitial fibrotic change, and honeycombing in advanced disease.13 In contrast to idiopathic pulmonary fibrosis, confluent ground glass changes are rare in asbestosis, whereas thick band-like opacities are more commonw8; the most discriminatory feature is concomitant pleural disease in asbestosis. Histological evidence is not necessary for the diagnosis to be made: typical clinical features along with previous asbestos exposure, consistent pulmonary function abnormalities, interstitial fibrosis (with no alternative explanation), plus other radiographic changes seen after exposure to asbestos are usually adequate. No specific treatment is available other than that for chronic obstructive pulmonary disease and cor pulmonale if present, smoking cessation, and prevention of further exposure to asbestos. The prognosis of asbestosis is highly variable and depends on the extent of lung involvement and severity of coexisting chronic obstructive pulmonary disease and presence of other comorbidities.
Fig 2 Computed tomograph showing typical features of asbestosis; note the peripheral interstial change
Malignant disease
Lung cancer
Exposure to asbestos causes lung cancer independently of cigarette smoking.14 w9 In an analysis of 23 epidemiological studies, asbestos exposure increased the risk of lung cancer by a similar factor in non-smokers and smokers, with a synergistic (multiplicative) interaction seen between asbestos exposure and cigarette smoking.14 Even in the absence of asbestosis, very heavy asbestos exposure may cause lung cancer.w10 Lung cancer should be considered in patients with asbestosis who have haemoptysis, worsening cough, chest pain and breathlessness, weight loss, and anorexia. Diagnostic and management strategies are the same as those for lung cancer in general (www.sign.ac.uk; www.nice.org.uk).
Mesothelioma
Malignant mesothelioma is an aggressive pleural tumour with increasing incidence.15, 16 Data from the UK mesothelioma register indicated that the annual number of deaths from mesothelioma had risen from 153 in 1968 to 1848 in 2001, and it is predicted to peak at 1950-2450 cases annually between 2011 and 2015.17 In 2006, the UK Health and Safety Executive gave the number of deaths from mesothelioma on death certificates as 2056 (85% male; www.hse.gov.uk/statistics/causdis/mesothelioma/).However, official mortality data may underestimate the extent by 10%.w11
In one well conducted study of 622 patients with mesothelioma (512 men), disease was caused by occupational or domestic asbestos exposure in 86% of men and 38% of women. Around half of the men were construction workers, and only four had worked for more than five years in the manufacture of asbestos products.4 The lag period between initial exposure and death varies, but one retrospective analysis (1105 patients with definite mesothelioma) found a median latency of 32 years, with 96% of cases occurring after at least 20 years.w12
The diagnosis of malignant mesothelioma is based on a combination of clinical, radiological, and histological features. However, a clear histological diagnosis removes any uncertainty and makes compensation claims more straightforward.
Clinical presentation
British Thoracic Society guidelines suggest that malignant mesothelioma should be considered in any patient with a pleural effusion or pleural thickening, especially if a history of asbestos exposure and chest pain is present.15 Characteristically, the pain is dull, diffuse, progressive, and occasionally pleuritic. Breathlessness may be caused by a pleural effusion or circumferential pleural thickening. Patients may also present with a palpable chest wall mass, finger clubbing (usually caused by underlying asbestosis), and features of a pericardial effusion caused by local extension in progressive disease. Ascites caused by peritoneal mesothelioma and secondary hydropneumothorax are uncommon but recognised presentations.
Investigations
Chest radiography and computed tomography may show a pleural effusion, lobulated or nodular pleural changes, a pleural mass, rib destruction, chest wall involvement, or a small hemithorax as a result of lung entrapment (fig 3); other features of exposure to asbestos may also be present.
Pleural fluid in patients with mesothelioma is straw coloured or blood stained. Cytological analysis of pleural fluid occasionally leads to the diagnosis, although a pleural biopsy is usually needed. Percutaneous pleural biopsy has historically been performed using an Abram’s needle,18, 19 although this procedure is no longer recommended because of the availability and superiority of ultrasound or computed tomography guided percutaneous biopsy.15 For example, in one study, 50 patients with a cytologically negative (although suspected malignant) pleural effusion were randomised to either Abram’s pleural biopsy or computed tomography guided biopsy.20 The first method correctly diagnosed malignancy in eight of 17 patients (sensitivity 47%, specificity 100%), whereas computed tomography guided biopsy diagnosed malignancy in 13 of 15 (sensitivity 87%, specificity 100%; difference in sensitivity between procedures 40%, 95% confidence interval 10% to 69%, P=0.02).An alternative surgical diagnostic procedure consists of a video assisted thoracoscopic approach that allows multiple biopsies to be taken under direct visualisation; this technique also allows talc pleurodesis to be performed at the same time if malignancy is highly likely. Thoracoscopy under local anaesthetic (enabling drainage of pleural fluid, biopsy, and pleurodesis) is becoming increasingly available across the UK and may be carried out by appropriately trained physicians.
Treatment
Patients with mesothelioma should be discussed at a lung multidisciplinary team meeting (comprising chest physicians, surgeons, radiologists, pathologists, oncologists, and specialist nurses; see box).15 w13 Although the benefits are uncertain, prophylactic radiotherapy to the pleural puncture site is often considered in patients who have had large chest wall incisions (during thoracoscopy or insertion of a large bore chest tube) to reduce the chance of tumour cells seeding along the track to the skin surface.21
Palliative chemotherapy is offered to fit patients, despite a paucity of data showing any survival advantage. In one study, 448 patients were randomised to receive pemetrexed plus cisplatin or cisplatin alone. Median survival with permetrexed and cisplatin was 12 months versus nine months with cisplatin alone (P=0.002).22 In another study of 250 patients,23 raltitrexed and cisplatin significantly improved overall survival compared with cisplatin alone, although no differences in quality of life were seen, and the study had no placebo arm. The role of surgery is controversial,24 but recent data suggest that extrapleural pneumonectomy is not useful in the management of mesothelioma25; however, the results of other trials are awaited (MesoVATS and MARS2).Lung sparing debulking procedures are now gaining popularity and should be considered for patients within the context of randomised trials.
The prognosis of malignant mesothelioma—especially in older men who are unfit and have peritoneal mesothelioma and sarcomatoid histology—is poor. The median survival in a variety of studies is between eight and 14 months from diagnosis.15
Patients with asbestos related lung disease may be eligible for compensation through Industrial Injuries Disablement Benefit (IIDB) from the Department of Social Security or a civil law claim for damages from the employer under whose auspices exposure occurred (table). Under the UK Limitation Act 1980, patients have only three years in which to make a civil claim from the date they became aware of a serious injury caused by an act or omission of the proposed defendant. Patients should be advised to consult their local Department of Work and Pensions benefit agency for advice on benefits that may be claimed (which may include attendance allowance and disability living allowance).Various charities can also provide help and support on compensation. Some compensation requests involve lengthy periods of negotiation (especially civil claims), and patients should be made aware of this to help minimise psychological distress. Former Ministry of Defence personnel who develop asbestos related diseases are unable to sue the crown for an industrial injury that occurred before 1987 because of “crown immunity,” although they may be eligible to receive a war pension.
Fig 3 Computed tomography showing typical features of mesothelioma (A, pleural based masses; B, pleural fluid; C, palpable chest wall mass; note the reduction in size of the left hemithorax)
*Currently, legislation in Scotland differs from that in the rest of the United Kingdom.
IIDB = Industrial Injuries Disablement Benefit; PWCA = Pneumoconiosis Workers’ Compensation Act 1979.
MANAGEMENT STRATEGIES IN MESOTHELIOMA
ADDITIONAL EDUCATIONAL RESOURCES
Additional resources for healthcare professionals
Resources for patients
TIPS FOR NON-SPECIALISTS
Thanks to Peter Montgomery for reviewing the section on compensation.
Contributors: GPC had the original idea for the manuscript and wrote it along with SJW and NAM. GPC is guarantor.
Competing interests: None declared.
Provenance and peer review: Commissioned based on an idea from the author; externally peer reviewed.
1 Wood WB, Gloyne SR. Pulmonary asbestosis. Lancet 1930;i:445.
2 Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 1960; 17: 260-71.
3 Tweedale G, Hansen P. Protecting the workers: the medical board and the asbestos industry, 1930s-1960s. Med Hist 1998; 42: 439-57.
4 Rake C, Gilham C, Hatch J, Darnton A, Hodgson J, Peto J. Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study. Br J Cancer 2009; 100: 1175-83.
5 Ferrante D, Bertolotti M, Todesco A, Mirabelli D, Terracini B, Magnani C. Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy. Environ Health Perspect 2007; 115: 1401-5.
6 Brody AR, Hill LH, Adkins B Jr, O’Connor RW. Chrysotile asbestos inhalation in rats: deposition pattern and reaction of alveolar epithelium and pulmonary macrophages. Am Rev Respir Dis 1981; 123: 670-9.
7 Merchant JA. Human epidemiology: a review of fiber type and characteristics in the development of malignant and nonmalignant disease. Environ Health Perspect 1990; 88: 287-93.
8 Mukherjee S, de Klerk N, Palmer LJ, Olsen NJ, Pang SC, Musk AW. Chest pain in asbestos-exposed individuals with benign pleural and parenchymal disease. Am J Respir Crit Care Med 2000; 162: 1807-11.
9 Lynch DA, Gamsu G, Aberle DR. Conventional and high resolution computed tomography in the diagnosis of asbestos-related diseases. Radiographics 1989; 9: 523-51.
10 Wagner GR. Asbestosis and silicosis. Lancet 1997; 349: 1311-5.
11 Wagner GR. The fallout from asbestos. Lancet 2007; 369: 973-4.
12 Kipen HM, Lilis R, Suzuki Y, Valciukas JA, Selikoff IJ. Pulmonary fibrosis in asbestos insulation workers with lung cancer: a radiological and histopathological evaluation. Br J Ind Med 1987; 44: 96-100.
13 Fletcher DE, Edge JR. The early radiological changes in pulmonary and pleural asbestosis. Clin Radiol 1970; 21: 355-65.
14 Lee PN. Relation between exposure to asbestos and smoking jointly and the risk of lung cancer. Occup Environ Med 2001; 58: 145-53.
15 British Thoracic Society. BTS statement on malignant mesothelioma in the UK, 2007. Thorax 2007; 62 (suppl 2): ii1-19.
16 Mak V, Davies E, Putcha V, Choodari-Oskooei B, Moller H. The epidemiology and treatment of mesothelioma in South East England 1985-2002. Thorax 2008; 63: 160-6.
17 Hodgson JT, McElvenny DM, Darnton AJ, Price MJ, Peto J. The expected burden of mesothelioma mortality in Great Britain from 2002 to 2050. Br J Cancer 2005; 92: 587-93.
18 Walshe AD, Douglas JG, Kerr KM, McKean ME, Godden DJ. An audit of the clinical investigation of pleural effusion. Thorax 1992; 47: 734-7.
19 McLaughlin KM, Kerr KM, Currie GP. Closed pleural biopsy to diagnose mesothelioma: Dead or alive? Lung Cancer 2009; 65: 388-98.
20 Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361: 1326-30.
21 Davies HE, Musk AW, Lee YC. Prophylactic radiotherapy for pleural puncture sites in mesothelioma: the controversy continues. Curr Opin Pulm Med 2008; 14: 326-30.
22 Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636-44.
23 Van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 2005; 23: 6881-9.
24 Treasure T, Utley M. Ten traps for the unwary in surgical series: a case study in mesothelioma reports. J Thorac Cardiovasc Surg 2007; 133: 1414-8.
25 Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg 2008; 135: 620-6.