Extrinsic Allergic Alveolitis and Isocyanates: A Case for Prescription?


Extrinsic allergic alveolitis (EAA) is a potentially serious lung condition arising from an allergic reaction in the smaller airways and gas-exchanging parts of the lung to a range of biological and chemical agents. Earlier this year, the Industrial Injuries Advisory Council (IIAC) published a report on EAA in which it concluded that the terms of prescription for EAA should be extended to include a class of chemicals called isocyanates. 

Within this feature article we will outline what EAA is, how it is contracted and which occupations are most commonly effected by the disease. Additionally, we will look at the report of the IIAC and consider how exposures to isocyanates were found to have sufficient causal links to achieve prescription for the purposes of the Industrial Injuries Disablement Benefit Scheme (IIDB). 


EAA, also known as hypersensitivity pneumonitis, happens when lungs develop an immune response (hypersensitivity) to something breathed in which triggers immune systems, causing short or long-term inflammation, especially in a part of the lungs called the interstitium. This inflammation makes it harder for the lungs to function properly and may even permanently damage the lungs. If diagnosed, some types of EAA are treatable by avoiding exposure to the environmental substances or with medicines such as corticosteroids that reduce inflammation. If the condition goes untreated or is not well controlled over time, the chronic inflammation can cause irreversible scarring of the lungs that may severely impair their ability to function.[i]


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In the lung interstitium, alveoli air sacs come into contact with the blood vessels and connective tissues of the lung. If you have EAA, your body’s immune system reacts strongly to certain inhaled substances, causing inflammation especially in the interstitium or interstitial space.

These substances include certain:

  • Bacteria and mycobacteria
  • Fungi or moulds
  • Proteins
  • Chemicals

Common environmental sources of substances that can cause EAA are:

  • Animal furs
  • Air conditioner, humidifier, and ventilation systems
  • Bird droppings and feathers
  • Contaminated foods such as cheese, grapes, barley, sugarcane
  • Contaminated industry products or materials such as sausage casings and corks
  • Contaminated metal working fluid
  • Hardwood dusts
  • Hay or grain animal feed
  • Hot tubs


The IIAC is an independent statutory body that advises the Secretary of State for Work and Pensions in Great Britain and the Department for Social Development in Northern Ireland on matters relating to the Industrial Injuries Scheme. The Scheme, Industrial Injuries Disablement Benefit (IIDB), provides compensation that can be paid to an employed earner because of the effects of an industrial accident or prescribed disease. In order for a disease to become a prescribed disease the Social Security Contributions and Benefits Act 1992 states that the Secretary of State must be satisfied that the disease:

  • Ought to be treated, having regard to its causes and incidence and any other relevant considerations, as a risk of the occupation and not as a risk common to all persons; and
  • Is such that, in the absence of special circumstances, the attribution of particular cases to the nature of the employment can be established or presumed with reasonable certainty. So, a disease may only be prescribed if there is a recognised risk to workers in an occupation, and the link between disease and occupation can be established or reasonably presumed in individual cases. Is epicondylitis a prescribed disease?

EAA has been a prescribed disease since 1964 when farmer’s lung due to ‘exposure to the dust of mouldy hay or other mouldy vegetable produce’ was scheduled. The terms of prescription were then extended in 1983 to include a list of other well-established causal agents and in 2006 to include cases caused by contaminated metalworking fluid which resulted in the terms of prescription as set out in the table below:

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Most cases of EAA, thus far, have arisen from biological agents causing allergies and so the prescribed disease has been classified as what is known as a ‘B’ disease i.e. a disease with a biological causation. However, it has been suggested that it is more common for the causal allergen to be a chemical and as such earlier this year the IIAC conducted another review of the condition and considered whether this prescription should be extended to include exposures to isocyanates and other chemicals and whether, because the list of recognised causal agents of EAA is ever growing, there should be an ‘open’ category of exposure akin to that used for prescriptions of occupational asthma.

Before we consider the chemical causation of EAA, let us review some of the biological prescriptions thus far.


As outlined above, EAA was first described in dairy farmers exposed to mouldy hay and was known as ‘farmer’s lung’. However, dust from any mouldy crop such as straw, corn silage, grain or even tobacco can also cause ‘farmer’s lung’.

However, following this discovery the Health and Safety Executive (HSE) have since claimed that the most common cause of EAA is through exposure to contaminated metal working fluid (MWF).[ii] MWF covers a wide variety of fluids used as lubricants or coolants for metal machining processes such as drilling, milling and turning and is also referred to as suds, coolant, slurry or soap.  Exposure to MWF can occur by direct contact with the skin, causing dermatitis or by inhalation, usually by way of mist generated during machining. It has been responsible for workplace outbreaks of EAA in the US over the last 15 years and has been seen more recently in the UK.

The association between EAA and exposure to MWF was discussed in the IIAC review of the topic in 2006.[iii] They found that EAA and exposure to MWF was initially described by Bernstein et al. (1995) in an outbreak in 6 American auto parts manufacturing workers. The phrase ‘machine operator’s lung’ was coined to describe the disease in line with other occupational causes of EAA. Since this first report, there have been a number of documented outbreaks of EAA associated with exposure to MWF within auto-parts manufacturing settings, mostly in America. The cases of EAA described in the literature shared similar clinical features. They had abnormal lung function tests, abnormal chest radiographs and symptoms of lung disease such as breathlessness, cough, wheeze, fatigue and fever. In certain cases, lung biopsy (the most definitive investigation) confirmed the characteristic pathological changes of EAA. Symptoms deteriorated if the worker was not removed from exposure to MWF and sometimes led to permanent decrements in lung function. Conversely, when affected workers were removed from the source of exposure their symptoms stabilized or improved.

Most of the evidence pointed to microbiological contamination of the fluid in use as the cause of adverse health effects. This proposition was supported by several bacterial and fungal species being isolated from MWF, some of which were determined as being potential causal. For example, in the US, evidence suggested that the nontuberculous mycobacterial species in contaminated MWF was involved in the toxic pulmonary changes associated with EAA.

The inhalation of aerosols of mycobacterial species were also implicated in the development of another form of EAA called ‘hot tub lung’.

The IIAC compared the link with mycobacterial species in the US to see if the same was found in the European outbreaks of EAA. They found that mycobacterial species have been less commonly isolated from contaminated MWF in Europe, which they said may reflect a difference in microbial flor or due to different culturing techniques.

Although they did report on three outbreaks of respiratory disease in engineering works in the UK – in Birmingham, South Yorkshire and Nottinghamshire. Work involving exposure to mists from MWF was common to all of the cases arising in the outbreaks which included occupational asthma (87 cases) and EAA (24 cases). The HSE conducted investigations into each of these incidences and concluded that in Birmingham:

‘…we now know that the cause of the disease was mist from metalworking machines, which was widespread throughout the factory. While we do not know the precise agent within the mist that triggered the outbreak, we did find links to bacteria, and used metalworking fluid. Other possible causes, such as metals leaching into the mist from the machining and washing of components, have been closely investigated and are thought unlikely to have caused the outbreak’.

As such the IIAC concluded in this report that where EAA occurs in a worker exposed to mists of MWF there is a strong presumption of occupational attribution in the individual case.

Some other antigens associated with EAA are encountered in an occupational setting and can be seen in the table below alongside the corresponding biological agent:

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As can be seen, there are many established biological exposures responsible for EAA, however, the IIAC have more recently considered the possible chemical exposure associated with the disease in particular the link with isocyanates.


Isocyanates are a family of reactive chemicals that have widespread applications. Most commonly they are used in polyurethane paints (hexamethylene diisocyanate), or in industrial glues or as a primary component in the manufacture of foam rubber or insulating materials (toluene diisocyanate and methylene diphenyl diisocyanate).

Many types of isocyanate vaporise easily and are thus readily inhaled. They are an important cause of occupational asthma, and in the UK suitable protection and regular health surveillance is mandatory for those whose work involves their use. Similarly they have also been linked to cases of Chronic Obstructive Pulmonary Disease (COPD). The HSE notes:

‘Workplace exposures likely to contribute to COPD include various dusts (including coal, grain and silica) as well as certain fumes and chemicals (including welding fume, isocyanates, and polycyclic aromatic hydrocarbons)’.[iv]

However, in 2007, the IIAC considered the case of COPD caused by isocyanates, and found that there was insufficient evidence for prescription. [v]


Isocyanates are also recognised to cause EAA and around 100 cases worldwide, acute and chronic, have been documented in the medical literature. These probably arise from more intense levels of exposure than those causing occupational asthma. There are several types of isocyanate which have been implicated.

One study, conducted by Baur,[vi] aimed to determine whether EAA is a common disorder in isocyanate workers by evaluating company physicians’ case histories of 1780 isocyanate workers. There were 14 individuals who had EAA and work-related dyspnea and fever occurring several hours after the start of work with isocyanates. Clinical findings of these workers included reduction of lung diffusing capacity, reticular or nodular lung patterns in the x-ray film and restrictive ventilation patterns in the inhalation challenge tests. It was concluded that exposure to isocyanate vapors and aerosols induces typical hypersensitivity pneumonitis in at least 1% of the isocyanate workers with symptoms. In this study, diphenylmethane diisocyanate was found to be the main cause of this disorder.

Where there has been a diagnosis of EAA and exposure to isocyanates, causal attribution is almost always made on the basis of symptoms, antibody tests in serum and characteristic functional and radiographic changes that follow exposure, with resolution once such exposure has ceased. Repeated experiences of this acute illness are common and are also a helpful pointer to the cause. Additionally, but very occasionally, provocation tests which involve experimental inhalation exposure under strictly controlled conditions have been used to demonstrate, directly, the link between isocyanate exposure and acute EAA. Most claimants of EAA are likely to be advised of their diagnosis by a respiratory specialist in circumstances where supporting clinical evidence will be available.

The IIAC concluded that EAA arising from isocyanates is uncommon in the UK with only six cases being linked to this kind of exposure between 1996 and 2004.


The IIAC also considered other established causes of EAA that are not presently covered by the current terms of prescription and noted that the list of recognised causes in the literature is regularly expanding with fungal and other biological allergens having been identified in a broad variety of workplaces, including sawmills, vineyards, sewage works, and sites where cheese and other foodstuffs are manufactured. Other chemical causes of EAA, such as acid anhydrides used in epoxy resins have also been identified, albeit very rarely.


The IIAC concluded that EAA is an uncommon disease and cases which occur in an occupational setting do so in response to airborne allergens in the workplace.[vii] Although they noted that EAA is one of a few prescribed diseases where prescription can be based on individual attribution with causal links between diagnosis and work being reasonably straightforward with specialist input.

Additionally it was acknowledged that there was evidence that high exposures to isocyanates of all types can give rise to acute and chronic EAA. As such it was recommended that the terms of prescription be amended both to recognise that exposure to the vapour of isocyanates can cause EAA and to create new open categories of exposure to other biological and chemical agents that can cause EAA.

Since Isocyanates are chemical and not biological agents, the IIAC created a new ‘C’ disease section within the prescription schedule and inserted the open category into the biological ‘B’ section as per the below:

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This approach may have the advantage of avoiding the need for repeated reviews of the terms of prescription for EAA, however, it may also offer future claimants of occupationally-caused EAA a more rapid route to benefits and could see an increase in volume of claims.


EAA arising from workplace exposures to isocyanates or other causal agents is a preventable illness.

The HSE notes that employers must identify tasks where employees will be using products containing isocyanates and ask themselves the following questions, is anyone in the area likely to be affected by the work being carried out including members of the public, which product is being used, how is the work being done and is it being done in an enclosed space?

Where possible, employees should think about eliminating or reducing isocyanate risks by using products that do not contain isocyanates or less volatile forms and avoiding unnecessary spraying. This causes more isocyanate to get into the air compared to using a brush or roller and being aware of anyone who is already sensitised to isocyanates.

The Control of Substances Hazardous to Health Regulations 2002 (COSHH) applies to work with isocyanates and other agents which can cause EAA. COSHH requires employers to undertake a suitable and sufficient assessment of the risks created by the work and to identify and take measures to prevent exposure as far as is reasonably practicable. Where it is not reasonably practicable to prevent exposure by substitution with a safer substance or total enclosure, exposure must be adequately controlled by the use of appropriate work processes, systems and engineering controls and measures including local exhaust ventilation systems to control exposure at source. Suitable respiratory protective equipment should also be used in addition where adequate control cannot otherwise be achieved.

Workers handling isocyanates and other established agents that cause work-related EAA need to be informed of the hazards/risks and be provided with appropriate training. In addition, COSHH requires employers to arrange appropriate health surveillance for EAA where employees are exposed to a substance known to cause the disease and there is a reasonable likelihood of it occurring under the conditions of work.


Usually, where a disease is not uniquely occupational and so indistinguishable from a disease occurring in someone that has not been exposed to a hazard at work, the IIAC require evidence of a doubling of the risk of developing the disease due to occupation.

For some diseases attribution to occupation may be possible from specific clinical features of the individual case. For example, the proof that an individual's dermatitis is caused by his occupation may lie in its improvement when he is on holiday, and regression when he returns to work, and in the demonstration that he is allergic to a specific substance with which he comes into contact only at work. It can be that the disease only occurs as a result of an occupational hazard.

This is the case with EAA and the prescribed exposures, where, the evidence is such that attribution can be made, or reasonably presumed, in the individual case on the basis of the clinical features. Therefore, evidence of doubling of risk is not required.

Despite the rarity of this disease, the extension of prescribed exposures in cases of EAA may result in higher volumes of claims in the future as established causes of the condition increase and become better known.


[i] British Lung Foundation, ‘Hypersensitivity Pneumonitis’ < https://www.blf.org.uk/support-for-you/pulmonary-fibrosis/hypersensitivity-pneumonitis> accessed 20th June 2017.

[ii] http://www.hse.gov.uk/lung-disease/extrinsic-allergic-alveolitis.htm

[iii] DWP, ‘Extrinsic Allergic Alveolitis’ (IIAC July 2006) Command Paper 6867.

[iv] Health & Safety Executive, ‘Chronic Obstructive Pulmonary Disease (COPD)’ http://www.hse.gov.uk/statistics/causdis/copd/ accessed 20th June 2017.

[v] Department for Work and Pensions, Chronic Obstructive Pulmonary Disease (COPD) – Chronic Bronchitis and Emphysema https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/243152/7253.pdf

[vi] Baur X, ‘Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis) Induced By Isocyanates’ (J Allergy Clin Immunol. 1995 May;95(5 Pt 1):1004-10.)

[vii] DWP, ‘Extrinsic Allergic Alveolitis: Isocyanates and Other Occupational Causes’ (IIAC April 2016) Command Paper 9247.