Asbestos consists of a family of naturally occurring hydrated silicate fibres that may be subdivided into two groups:
• Curly serpentine fibres, of which chrysotile (white) is the only fibre currently in commercial use
• Straight needle-like amphiboles, which comprise crocidolite (blue), amosite (brown), anthophyllite, tremolite, and actinolite.
Fibres have a predisposition to localize to the pleura. They differ in their lung clearance kinetics and pathogenic potential; amphibole fibres clear more slowly from the lung and are more carcinogenic than chrysotile. Whilst asbestos usage in developed countries is restricted, the use of chrysotile asbestos in developing economies continues to rise.
Mechanisms of exposure
accounts for the majority of cases of asbestos-related disease and includes:
• Mining, milling, and transport of asbestos
• Use of asbestos products, e.g. in construction and demolition, floor tiling, insulation, fireproofing, textiles, friction materials (brake linings), ship building, pipefitting, electrical repair, boiler fitting and lagging, carpentry, plumbing, and welding.
• Relatives of asbestos workers exposed to ‘carry home’ asbestos in hair or clothes
• Following remodelling or renovation in contaminated buildings
• Local geological exposure from natural deposits, e.g. areas of central and south-east Turkey, north-west Greece, and Corsica
• Urban environment (although undisturbed and non-friable asbestos building insulation is not considered hazardous).
A complete occupational history is essential if asbestos-related disease is suspected and should include the method of exposure, with dates and names of employers. This information may be of medicolegal importance and ideally should be elicited during the first consultation.
Asbestos-related lung disease
• Benign asbestos-related pleural disease
• Pleural plaques
• Benign asbestos-related pleural effusion
• Diffuse pleural thickening
• Rounded atelectasis
• Lung cancer (multiplicative risk from smoking).
Other diseases linked to asbestos exposure include pericarditis and perhaps head and neck and GI cancers. Whether asbestos exposure truly leads to an increased risk of lung cancer in the absence of asbestosis remains controversial.
Asbestos-related disease typically exhibits a long latency period of 20–40y from exposure. Peak industrial asbestos use in the UK occurred in the early 1970s, and asbestos-related disease is likely to remain common for at least the next 20y. The incidence of mesothelioma is forecast to peak in 2015–2020 in Europe.
All deaths should be notified to the coroner if asbestos-related disease is suspected or proven.
• Most common manifestation of asbestos exposure
• Discrete areas of white or yellow thickening on the parietal pleura; may calcify. Histologically, these are acellular, avascular areas of hyaline collagen fibrosis
• Bilateral and occur particularly on the posterolateral chest wall (particularly adjacent to ribs), over the mediastinal pleura, and on the dome of the diaphragm but are absent in the costophrenic angles
• Develop 20–30y after exposure; incidence (but not the extent of plaques) increases with longer duration of exposure; found in up to 50% of asbestos-exposed workers and may also occur after low-dose exposures
• Usually asymptomatic although, if extensive, may be associated with mild breathlessness due to pleural restriction
• Effect on pulmonary function is uncertain: most studies have failed to demonstrate abnormal lung function, although otherwise unexplained mild airways obstruction or restriction has been described in some populations of asbestos workers with pleural plaques—the mechanism of this is unclear, although it may reflect asbestos-induced small airway disease or early interstitial fibrosis, respectively
• HRCT is more sensitive than CXR in detecting pleural plaques
• There is no evidence that plaques are pre-malignant
• TB, trauma, and haemothorax may each cause single pleural plaques; multiple plaques are highly suggestive of asbestos exposure.
Benign asbestos-related pleural effusions
• Relatively early manifestation of asbestos pleural disease; usually occurs within 10y of exposure
• Development is considered to be dose-dependent although can occur after minimal exposure
• Typically small and unilateral and may be asymptomatic or occasionally associated with pleuritic pain, fever, and dyspnoea
• Usually resolve spontaneously over a few months, although some recur
• The pleural effusion is an exudate, often bloodstained, with no characteristic findings on pleural fluid analysis
• Diagnosis depends on a history of asbestos exposure and the exclusion of other causes, including mesothelioma
• Benign asbestos pleurisy may precede the development of diffuse pleural thickening; there is no clear association with mesothelioma
• Treat symptomatically, with pleural aspiration for breathlessness and NSAIDs for pain.
• Consists of extensive fibrosis of the visceral pleura, with areas of adhesion with the parietal pleura and consequent obliteration of the pleural space
• Unlike pleural plaques, its margins are ill-defined, and it may involve the costophrenic angles, apices, and interlobar fissures
• Development appears to be dose-related and may follow recurrent asbestos pleurisy
• On CXR, it may be defined as a smooth, uninterrupted pleural opacity, extending over at least a quarter of the chest wall, with or without obliteration of the costophrenic angles; on CT, the pleural density extends >8cm craniocaudally, 5cm laterally, and is >3mm thick
• Symptoms are relatively common and comprise exertional breathlessness and chest pain, which can be chronic and severe
• May lead to significant restrictive pulmonary function impairment, especially if the costophrenic angle is obliterated; hypercapnic respiratory failure has been described
• Pleural biopsy may be required to distinguish it from mesothelioma
• Treatment is difficult; decortication often fails to result in clinical or functional improvement
(Also known as folded lung, Blesovsky syndrome, or shrinking pleuritis with atelectasis.)
• Develops as contracting visceral pleural fibrosis; ensnares and then twists the underlying lung, resulting in the distinctive radiological appearance of a rounded or oval pleural-based mass of 2.5–5cm in diameter
• Asbestos exposure is the most common cause, although any cause of pleural inflammation may result in rounded atelectasis
• CT is often diagnostic, demonstrating a ‘comet tail’ of vessels and bronchi converging toward the lesion, adjacent thickened pleura, and volume loss in the affected lobe
• An atypical appearance may require biopsy to exclude malignant disease
• Typically asymptomatic, although breathlessness or dry cough may occur
• Usually stable or slowly progressive, and no specific treatment is required
• Surgical decortication may improve symptoms but frequently results in reduced lung volumes and is not generally recommended.
Factors affecting disease development include:
• Degree and length of asbestos exposure A clear dose-response relationship exists; usually seen in workers with many years of high exposure although may follow a very high exposure of short duration, resulting in a shorter latency period
• Fibre type Amphibole fibres are probably more fibrogenic than chrysotile, although most exposures are mixed fibre types
• Cigarette smoking increases the severity and rate of progression of asbestosis.
Latency period from first exposure to clinical disease is usually at least 15–20y and may be >40y.
Insidious onset of breathlessness, dry cough. Bibasal late-inspiratory crackles, clubbing in 40% of cases. May progress to respiratory failure, cor pulmonale.
• CXR Bilateral symmetrical reticulonodular pattern, primarily affecting the lower lobes peripherally, which may extend upwards to involve the mid- and upper zones; may progress to honeycomb lung. Massive bilateral upper lobe fibrosis (without lower lobe involvement) is rare but well described. Associated pleural thickening or plaques may be seen and suggest a diagnosis of asbestosis, rather than UIP. Classification is based on size, thickness, and profusion of opacities. CXR insensitive to early disease; may be normal in 15–20% of symptomatic biopsy-proven asbestosis
• HRCT is more sensitive than CXR and is abnormal in 10–30% of cases with a normal CXR. Features include basal ‘ground-glass’ opacities (seen early in the disease), parenchymal bands, subpleural curvilinear lines and opacities, interlobular septal thickening, and signs of fibrosis (traction bronchiectasis, loss of lobular architecture, honeycombing in advanced disease)
• PFTs are classically restrictive with reduced lung volumes and transfer factor, although obstructive or mixed patterns may also occur (perhaps reflecting asbestos-induced small airway disease)
• Positive gallium scan may be seen with normal CXR; correlates poorly with lung function
• Analysis of sputum or BAL may demonstrate asbestos bodies, although sensitivity is limited. The finding of interstitial fibrosis, in the absence of asbestos bodies, on lung biopsy makes asbestosis unlikely. Analysis of material for asbestos bodies is only very rarely indicated, usually for research or litigation purposes.
In general, CXR and HRCT show only limited correlation with physiological disease severity.
Gold standard is pathological demonstration of fibrosis with mineralogical quantification of asbestos bodies. The College of American Pathologists and Pulmonary Pathology Society have defined a 5-point scheme for grading asbestosis:
• Grade 0—fibrosis confined to bronchiolar walls
• Grade 1—fibrosis extends only to first-tier alveoli
• Grade 2—fibrosis involves alveolar ducts and second-tier alveoli
• Grade 3—fibrosis of all alveoli between respiratory bronchioles
• Grade 4—honeycombing.
In practice, histology is rarely required, and a diagnosis can be made on the basis of a history of significant asbestos exposure, with appropriate delay between exposure and disease, and radiographic evidence of fibrosis (particularly when seen with pleural plaques).
varies widely. After removal from exposure, progression occurs in 5–40% of patients over 10y; progression is faster following greater exposure, although rapid progression over 1–2y is unusual and more in keeping with UIP. Fewer CXR opacities after exposure are associated with better prognosis. Increased risk of developing lung cancer.
Malignant tumour of mesothelial surfaces (most commonly the pleura), usually resulting from asbestos exposure.
Asbestos is the major single cause, and there is a history of occupational asbestos exposure in up to 90% of cases. All types of asbestos can cause mesothelioma—amphibole is the most potent, but also evidence for chrysotile. Mean latent interval between first exposure and death is around 40y; cases with latency <15y are rare. Not dose-related (unlike asbestosis or bronchogenic cancers) and no evidence for a threshold asbestos dose below which there is no risk, although the risk at low exposure levels is small. No significant association with smoking. The mechanism through which asbestos fibres result in mesothelioma is unclear; possibilities include direct irritation of the parietal pleura, disruption of mitosis, generation of toxic O2 radicals, and stimulation of mitogen-activated kinases leading to proto-oncogene activation.
Other causes of mesothelioma include non-asbestos fibres, such as erionite, which is found in rocks in Cappadocia, Turkey—mesothelioma accounts for up to a quarter of all adult deaths in local villages. Evidence for Simian Virus 40 (contaminated polio vaccine in 1950s/60s) is limited. Rare cases of mesothelioma caused by ionizing radiation or chest injury are described. ‘Spontaneous’ mesothelioma in children is also documented.
of pleural mesothelioma:
• Chest pain (typically dull ache, ‘boring’, diffuse, occasionally pleuritic), breathlessness; a small proportion are asymptomatic. Profuse sweating may occur
• Consider in any patient with a pleural effusion or pleural thickening, particularly if chest pain is present
• Rarely may present with persistent chest pain and a normal CXR
• Weight loss and fatigue uncommon at presentation (<30% of cases)
• Clubbing is very rare (<1%)
• Chest wall invasion may be seen (especially at thoracentesis sites)
• Bilateral pleural involvement is unusual at presentation
• Paraneoplastic syndromes are described, e.g. DIC.
includes benign asbestos pleural effusion, DPT, and adenocarcinoma involving the pleura.
aspiration typically reveals an exudative straw-coloured or bloody effusion. Cytological analysis may provide the diagnosis (sensitivity range 32–84%) and is often useful in excluding other pathology, e.g. adenocarcinoma. Poor at diagnosing sarcomatoid mesothelioma. Pleural fluid glucose and pH may be low in extensive tumours. Mesothelioma may track through the chest wall along thoracentesis sites; avoid repeated pleural aspiration if the diagnosis is suspected.
CXR and CT features include:
• Localized pleural mass or thickening without free fluid
• Uniform encasement of lung, resulting in small hemithorax
• Local invasion of chest wall, ribs, heart, mediastinum, hilar nodes, and diaphragm; transdiaphragmatic spread and invasion of contralateral pleura
• Associated pleural plaques or interstitial fibrosis in a minority of cases.
The role of MRI is unclear—it may provide additional information in some cases, e.g. chest wall invasion, although is rarely required. PET-CT may have a role in distinguishing benign and malignant pleural disease, as well as identifying lymph node spread for staging, and can help to select sites for image-guided biopsy.
Diagnosis usually requires histological confirmation, except when the patient is too unwell or too frail for biopsy. US- or CT-guided cutting needle biopsy and thoracoscopic biopsy of pleural masses have a high diagnostic yield and should be used in preference to blind (Abrams’) biopsy techniques. Early use of thoracoscopy may both provide a diagnosis and enable treatment of large effusions with talc pleurodesis, thereby avoiding repeated non-diagnostic procedures with attendant problems of needle-track spread.
• Epithelioid (50% of cases; may be confused with adenocarcinoma; better prognosis)
• Sarcomatoid (or fibrous; includes lymphohistiocytoid and desmoplastic patterns)
• Mixed (biphasic; contains both subtypes).
Immunohistochemistry is key to making the diagnosis. Stains which are positive for mesothelioma include calretinin, EMA (CA15-3/mucin-1– dense peripheral staining pattern), keratin CK5/6, WT-1, and podoplanin. Stains that are usually negative for mesothelioma include CEA, TTF-1, B72.3, CD15 (usually positive for lung adenocarcinoma), ER (usually positive for breast carcinoma), and p63 (squamous cell carcinoma). Electron microscopy of histopathological specimens may also help to distinguish mesothelioma from adenocarcinoma.
No widely accepted staging system. The International Mesothelioma Interest Group (IMIG) system is commonly used and gives stages I–IV, based on TNM classification. Imaging may underestimate extent of disease, and accurate staging would require surgical exploration. Poor prognostic features include transdiaphragmatic muscle invasion and involvement of mediastinal lymph nodes, ♂ gender, age >75, chest pain, poor performance status, high WCC, thrombocytosis, and non-epithelioid histology. A low standardized uptake value (SUV) on PET may also be prognostically beneficial.
Management of pleural effusions
Early definitive treatment is key; repeated pleural aspirations should be avoided. Talc pleurodesis can be achieved either using a chest drain or at thoracoscopy, depending on local resources. Pleurodesis is not possible if the lung does not re-expand following drainage of pleural fluid (‘trapped lung’) and the resulting recurrent pleural effusions are difficult to manage; indwelling pleural catheters (IPCs) allow fluid drainage without needle aspiration and are useful in this situation. A recent RCT suggested that 1° use of IPCs was reasonable, dependent on patient preference (see p. [link]).
Prophylactic radiotherapy appears to reduce chest wall invasion by tumour following large-bore chest drain insertion or biopsy: three fractions reduced the risk of tracking from 40% to 0 in a randomized study of 40 patients, although a subsequent study failed to demonstrate a benefit. Recurrence may follow delayed prophylactic radiotherapy, so it is usually administered within 4 weeks. Palliative radiotherapy provides pain relief in a proportion of patients with chest wall pain but is less useful in the treatment of breathlessness or SVCO.
Four types of surgery have been used—extrapleural pneumonectomy (EPP), pleurectomy with decortication (PD; lung-sparing, may help with re-expansion of trapped lung), limited pleurectomy, and thoracoscopy with pleurodesis, but their roles require further investigation. Trimodal therapy (chemotherapy, followed by EPP and radiotherapy) was evaluated in the MARS randomized feasibility study for ‘resectable disease’, finding the EPP group to have a shortened survival without any gain in QoL, although the study has been controversial. Operative mortality is ± 7–16% for EPP and ± 4% for PD. Results are awaited from a further study comparing talc pleurodesis vs VATS pleurectomy (MesoVATS).
Patients with good performance status should be considered for chemotherapy. Pemetrexed (an inhibitor of DNA synthesis proteins, e.g. thymidylate synthase) plus cisplatin has an objective response rate (tumour shrinkage of >50%) of 41% and appears to convey a survival advantage of just under 3 months when compared with cisplatin alone. Since the National Institute for Health and Clinical Excellence (NICE) approval of pemetrexed in 2008, cisplatin/pemetrexed combination is a frequently used combination, although carboplatin may be substituted for cisplatin in those at increased risk of toxicity. Ongoing treatment of an individual may be guided by objective metabolic responses based on PET-CT. Other studies have shown that addition of raltitrexed to cisplatin improves surival by 2.5 months, and gemcitabine plus cisplatin led to objective response rates of 33 and 48% in two trials, with QoL benefits. Trials are ongoing.
Early involvement of a pain relief and palliative care service is required. Ensure adequate analgesia: opiates and non-steroidal anti-inflammatory drugs (NSAIDs) for chest wall pain; consider amitriptyline, pregabalin, or gabapentin for neuropathic pain (from intercostal nerve or vertebral involvement); nerve blocks or cordotomy may be required. Breathlessness may be multifactorial, e.g. pleural effusion, lung compression, chest wall restriction, pericardial involvement, anaemia, pain, anxiety, and fear. Discuss compensation issues (see pp. [link]–[link]). Liaise with GP, specialist nurse, palliative care teams. Remind GP that all deaths have to be reported to the coroner. The Coroners’ Society of England and Wales and the British Thoracic Society (BTS) have encouraged coroners to avoid post-mortems where biopsy has already confirmed mesothelioma. A coronial inquest is opened and adjourned soon after death but may take ± 3 months for the full inquest to complete.
Median survival is 4–12 months from diagnosis. Typically progresses by local extension, sometimes leading to involvement of the contralateral lung or peritoneum, SVCO, cardiac tamponade, or spinal cord compression. Distant metastases are common (50% at autopsy), although occur late and are rarely clinically apparent.
is rarer than pleural mesothelioma and may be associated with more prolonged asbestos exposure. Remains intra-abdominal in most cases. Clinical features include abdominal discomfort, weight loss, ascites, and, in some cases, organ involvement (e.g. intestinal obstruction). FNA of omental masses may provide a diagnosis, although laparoscopy is often required. Prognosis is worse than for pleural mesothelioma, with median survival 7.4 months. No treatment is of proven benefit.
Mesothelioma has also been described affecting other serosal surfaces such as pericardium and tunica vaginalis.
• Several biomarkers have shown promise in mesothelioma diagnosis, but none are recommended as sole diagnostic tests. Mesothelin (expressed on the surface of mesothelial cells) is an FDA-approved diagnostic and prognostic marker for mesothelioma, with a sensitivity of 48–84% and specificity of 70–100%. Other malignancies can raise levels (including ovarian, pancreatic, and lung carcinomas, lymphoma). Other potential markers include megakaryocyte-potentiating factor (MPF) and osteopontin
• Microarray studies of gene expression in tumour samples may prove to be useful in both distinguishing mesothelioma from adenocarcinoma and in predicting prognosis
• Novel therapeutic strategies using immunotherapy (e.g. antimesothelin monoclonal antibodies), gene therapy, anti-angiogenic agents, and photodynamic therapy are in development. Combinations of immunotherapy with chemotherapy appear particularly promising.
BTS statement on malignant mesothelioma in the United Kingdom. Thorax 2007;62:ii1–ii19.Find this resource:
Scherpereel A et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J 2010;35:479–95.Find this resource:
Identification of asbestos exposure is essential for the patient to be able to claim compensation. Patients are not eligible for compensation if their exposure occurred whilst they were self-employed. There are two principal sources of support and compensation.
From the government
Apply to the Department for Work and Pensions for Industrial Injuries Disablement Benefit, using form BI100PD (health care team fill in form BI100PN(A)). Available for the following diseases:
• Lung cancer associated with DPT or asbestosis or some asbestos exposure.
There must be a clear history of asbestos exposure at work. Compensation is not available for pleural plaques alone. If successful and employer is no longer in business, may apply for a single payment from the government under the Pneumoconiosis, etc. (Worker’s Compensation) Act 1979. The value of compensation reflects the degree of disability from which the patient is considered to suffer and their age at diagnosis. Next of kin may also claim within 6 months posthumously. Other benefits may be available, including Diffuse Mesothelioma Payment (for patients who have had secondary asbestos exposure from their partner, and the self-employed), Constant Attendance Allowance, Exceptionally Severe Disablement Allowance, and Reduced Earnings Allowance. The War Disablement Pension scheme may provide compensation for disease resulting from asbestos exposure with HM forces.
From the courts: Civil law
compensation directly from a previous employer. Can be claimed from the employer’s insurer, even if the employer is now out of existence. Advise patient to seek advice as soon as possible from a solicitor with relevant experience. Claims must be initiated within 3y of the individual’s first awareness that they have an asbestos-related disease; attempts to initiate claims after 3y may be statute-barred. Inform the patient of this, and document the conversation in the medical notes. In England and Wales, a Court of Appeal ruling in 2006 concluded that pleural plaques alone should now no longer be considered an indication for compensation, and a subsequent 2007 appeal failed to overturn this ruling in the House of Lords. Subsequent 2011 legislation in Scotland and Northern Ireland has made plaques compensable in these countries. Awards for asbestosis range from £15, 000 to £50, 000, depending on symptoms and the degree of disability; such patients may accept an interim settlement, allowing further claims to be made, or may wish to take a greater ‘once and for all’ award and forego their right to further claims in the event of mesothelioma developing. Typical awards for mesothelioma are £45, 000–£50, 000, with additional amounts awarded for care and future loss of wages and pension; total compensation may be ± £100, 000 (or significantly more for younger patients). Successful claims have also been made for mesothelioma occurring in relatives who had 2° exposure to asbestos whilst washing work clothes.
Benefits Enquiry Line 0800 882200. Advice on available benefits and completing claim applications. Guide to Industrial Injuries Disablement Benefits (DB1) gives guidance on IIDB, Pneumoconiosis, etc. (Worker’s Compensation) Act 1979 and other benefits: http://www.dwp.gov.uk/publications/specialist-guides/technical-guidance/db1-a-guide-to-industrial-injuries/; http://www.gov.uk/industrial-injuries-disablement-benefit.