Aetiology

Sensitiser-induced occupational asthma (OA) is presumed to occur through exposure and immunological sensitisation to a specific work agent in a genetically predisposed worker.​[34][35]​​​​

Specific immunoglobulin E (IgE) antibodies to high molecular weight sensitisers (e.g., industrial enzymes, latex), and a few low molecular weight chemical sensitisers (e.g., diisocyanates), have been demonstrated in association with OA.​[36][22]​​​​​​​ In patients with an appropriate history and objective pulmonary function support for asthma, demonstration of specific IgE antibodies to the workplace sensitiser associated with symptoms has strong positive predictive value.[37]​ IgE antibodies to sensitisers may, however, be demonstrated in a proportion of asymptomatic exposed workers.[36][38]

For many chemical agents, specific sensitisation is not associated with demonstrable specific IgE antibodies to that agent. Explanatory hypotheses postulate that a relevant allergen has not been identified for specific testing, that an allergen is formed only after interaction with host proteins or other molecules (e.g., in the respiratory tract), or that skin exposure may be a route for initial sensitisation (e.g., to some less volatile diisocyanates). Other, as yet unclear, non-IgE immunological mechanisms may play a role. For example, peripheral blood mononuclear cell chemokine stimulation has been demonstrated in patients with OA from diisocyanates.[39]​ 

Irritant-induced OA can result acutely from a high-level inhaled irritant exposure, resulting in an airway inflammatory response. If the exposure agent is also a potential sensitiser (e.g., a spill of toluene diisocyanate) then the high-level exposure may potentially also cause specific sensitisation. However, most irritants do not cause a specific immunological response, and subsequent re-exposure within allowable occupational exposure limits are not expected to trigger worsening of asthma more than that for patients with a similar severity of non-occupational asthma.

Less acute onset of asthma following exposure to an irritant (e.g., starting after several days or more) may be due to that exposure, but it may be difficult to establish this with any certainty.[4] Chronic low/moderate-level exposure to irritants at work may also be associated with new-onset asthma.[4][40]

Pathophysiology

Pathological changes within the respiratory tract in sensitiser-induced OA cannot be distinguished from other asthma. Most patients have eosinophilic airway inflammation, as demonstrated by induced sputum cytology. In those with sputum eosinophilia, the percentage of eosinophils increases during a period of exposure to the sensitiser and lessens without exposure. This feature is useful diagnostically.[41][42]

A few patients have only occupational eosinophilic bronchitis without other asthma manifestations.[43] A minority of patients with sensitiser-induced OA have a neutrophilic inflammatory response in the airways; this has been more commonly reported with OA from low molecular weight sensitisers than from high molecular weight sensitisers. There are often some differences in clinical features between sensitiser-induced OA caused by low molecular weight and high molecular weight agents.[29]

Lung function changes are similar to those with other asthma. This includes airflow limitation (as shown on spirometry and serial peak flow recordings) and increased airway responsiveness (as demonstrated by methacholine challenge). In patients with OA, lung function worsens at work and often improves away from exposure to the causative agent. It can take several months away from exposure for lung function to improve. Improvement may, however, occur within a few days away from exposure, potentially resulting in return to normal spirometry and methacholine response. Therefore, assessment of suspected sensitiser-induced OA should ideally occur when the patient has recently been exposed to the suspected sensitiser and has recently experienced asthma symptoms.[22]​​

Irritant-induced asthma

Inhalation of an irritant compound is thought to induce bronchial epithelial damage, leading to increased lung permeability and remodelling of the airway epithelium via inflammatory mechanisms.[4][44]​​ Asthma symptoms, airflow limitation, and airway hyper-responsiveness may improve progressively over time, with resolution of asthma in some patients. However, in other patients clinical features of asthma may persist long-term.[22]​​

Generally, irritant-induced asthma has no diagnostic pathology that differs from that of other asthma. Results from one cross-sectional study suggested that irritant-induced asthma is associated with signs and symptoms including respiratory symptoms, poor lung function, high level of fluorescent oxidation products, and high neutrophil count.[45]

Classification

Definition and classification of asthma in the workplace[3][4]

Work-related asthma

  • Work-exacerbated asthma (aggravated by, but not caused by work)

  • Occupational asthma (caused by work)

    • Sensitiser-induced OA (caused by a specific immunological response)

      • Caused by high molecular weight agents (usually associated with specific IgE antibodies)

      • Caused by low molecular weight agents (usually chemical agents and less commonly associated with demonstrable specific IgE antibodies)

    • Irritant-induced OA (most clearly identified when caused acutely by a high-level irritant exposure).

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