The exposures encountered by research workers are as numerous and varied as the research they do. Thus the term ‘research worker’ is a broad one and encompasses a very wide range of individuals with an unusually wide range of potentially hazardous exposures. Moreover, at least in economically developed countries, the total population of research workers is large. Many researchers will be working in universities or other places of higher education – in some cities these are major employers with many thousands of research staff. Others will be employed in the research departments of the commercial sector, often in the pharmaceutical or biotechnology fields; again these workforces are often large although there is an increasing trend, particularly in the biotechnology sector, towards small companies employing just a few research staff. The term ‘research worker’ might also be applied to those who work in developmental or quality control laboratories within industry.

In this context, any meaningful clinical assessment of a potentially ‘occupational’ lung disease will require close attention to particular exposures relating both to materials that are used in primary research and those that represent finished products. In many cases such exposures will be obvious; these include, for example, research work with laboratory animals, the use of chemicals widely recognized to cause respiratory irritation and the wearing of latex gloves. Other exposures will be more obscure and will require careful questioning and/or consultation of reference information obtainable either through an employer or directly from the producers or suppliers of chemical agents.

Research workers are, in general, highly educated and highly motivated. They will have a better understanding of their work than will their clinician; at the same time they may have a mildly cavalier attitude to the hazards associated with their work, especially if they have been involved in it for many years. Many will be reluctant, at least initially, to consider an occupational etiology for their disease and more reluctant still to consider leaving or changing their work; this poses special difficulties for those who have developed an occupational hypersensitivity. On the other hand their levels of education – and the relatively liberal environments where they work – mean that career options are often wider than for those who work in industry. Most institutes of higher education and most large companies involved heavily in research will have a well organized system of occupational healthcare including regular health surveillance. Thus their employees are, in this respect, relatively well supported. Furthermore, most research settings are carefully regulated and most research processes are on a fairly limited scale. For these reasons, researchenvironment exposures – with some exceptions, notably those relating to laboratory animals – tend to be considerably less intense than those encountered on the shop floor.

The clinical manifestations of laboratory animal allergy are well recognized and are instructive. They probably apply to most other causes of respiratory sensitization among research workers:

• Most cases arise within two years of first exposure, a reflection of the responsible immune process and of innate individual susceptibility. It is unusual for a laboratory animal researcher to develop disease after many years of similar work. Beware, however, the researcher who has been employed for many years but has recently started work with a different species or process, and the researcher who has elected previously to deny the presence of work-related symptoms.
  
• For much the same reasons, laboratory animal allergy does not generally manifest within the first few months of exposure. This period of latency is an important clinical clue to the distinction of ‘occupational’ asthma from the exacerbation of asthma due to another cause.
  
• Symptoms of asthma due to animal sensitization are universally accompanied by nasal and eye symptoms similar to those that characterize hayfever. Thus the absence of eye and nose symptoms at work makes a diagnosis of laboratory animal asthma improbable.
  
• Both lower and upper respiratory symptoms are related to exposures at work in as much as they are provoked by being at work and are, at least in early cases, relieved when away from work. Immediate (‘early’) symptoms may be accompanied by those that occur later (‘delayed’), perhaps while at home after work. This can give rise to some diagnostic confusion. In more chronic cases there may be relatively little – or no – relief when away from work, a reflection of ongoing bronchial and nasal hyper-reactivity.
  
• Similarly, hyper-reactivity as a result of immunological sensitization may also give rise to symptoms on contact with nonspecific and nonoccupational irritant exposures such as perfumes or cold air; again this may confuse the clinical picture.
  
• Laboratory animal asthma – and most cases of laboratory animal rhinoconjunctivitis – is almost always accompanied by evidence of specific immunological sensitization. This is characterized by the production of specific IgE antibodies and is detectable by skin prick testing with appropriate allergens or by measurement of specific IgE antibodies in serum. Suitable reagants for many animal species are available commercially but in more unsusual cases it may be necessary to communicate directly with an experienced laboratory. For small mammals, testing with urinary antigens is more sensitive than testing with epithelial extracts. Skin prick testing should include the use of positive and negative control solutions; the latter is especially important to avoid false positive findings.
  
• Once sensitized, patients with laboratory animal allergen may be exquisitely sensitive to even very small concentrations of airborne allergen. This is reflective of the hypersensitive immunology that gives rise to the disease; it can make management of an individual case very difficult.

The diagnostic process in research workers suspected of laboratory animal allergy reflects the manifestations and processes listed above. History taking requires careful attention to the nature and duration of appropriate exposures. It is helpful especially to enquire:

• What exactly is their occupational contact with animals in terms of direct handling of live, anesthetized or dead animals? Are they handling only harvested tissues? For how long and how frequently do they have such contact? Does their work include cleaning cages or the handling of bedding or foodstuffs? In occasional cases sensitization arises not from animal proteins but from biological material used as feed.
  
• How often are they in the animal facility without direct animal contact? Is their animal work only within the animal house or do they also carry out experiments in other laboratories?
  
• How close and how often are they working to and with others who handle animals? Similarly, is this only within the animal house or does it occur in other settings?
  
• Do they wear latex gloves when working with animals? Where powdered gloves are (or have been) used, then these may be responsible for immune sensitization (latex allergy) rather than the animal species which they are used to handle.
  
• Do they wear protective respiratory equipment when working with animals? How often do they wear it – and how often is it serviced? Are simple half-face masks re-used and in any case do they fit properly? Some animal research facilities require the use of powered full-face ventilators; if used routinely and properly, these are extremely effective in reducing exposures to airborne allergens.
  
• What has been their previous experience with laboratory animal work – including as an undergraduate? Do they – or have they in the past – kept similar animals as pets at home? Pet rats, for example, are remarkably adept at inducing sensitization in their domestic owners.

While it is possible to measure air levels of, and personal exposures to, animal allergens within the laboratory the methodology is complicated, poorly standardized and seldom if ever useful in clinical practice.

In the same way as above, a careful account of the character, latency and timing of symptoms is crucial. Here, helpful information includes:

• A history enquiring into previous respiratory allergy – even if quiescent at the time of starting work. It is of course perfectly possible to acquire an occupational asthma or rhinitis on the back of a prior history of such allergic disease; disentangling the two can be difficult.
  
• The timing of first symptoms at work. Those that begin very shortly after starting a new job are likely to reflect the provocation of pre-existing disease or asymptomatic bronchial hyper-reactivity. Those that start several months later are more likely to reflect immune sensitization.
  
• The use of asthma or nasal treatments and an assessment of the degree of control of any pre-existing condition.
  
• The co-existence of work-related nasal and lower respiratory symptoms and their relative timing of onset. Classically in laboratory animal allergy rhinitis is reported before the onset of asthma symptoms.
  
• The current temporal relationship between symptoms and work. Recall that any improvement away from work may be less obvious if symptoms have been present for a long time.
  
• The current temporal relationship between symptoms and specific tasks at work. Advantage can be taken of the often very variable daily schedule of many research workers. Note that patients with bronchial hyper-reactivity may relate their symptoms to irritant exposures at work. Most respiratory irritants do not induce specific sensitization and reactions to them may reflect an immunologically induced bronchial hyper-reactivity to another agent.

It is unwise to make a diagnosis of animal allergy on the basis of a history alone; such a practice will inevitably give rise to false positive diagnoses. In the presence of a characteristic history from an animal research worker with appropriate exposure, the next step is the establishment or otherwise of specific sensitization using, as above, either skin prick testing or measurement of serum specific IgE antibodies – or preferably both. The absence of an identifiable IgE response – assuming this has been done rigorously – should prompt serious consideration of an alternative diagnosis.