Case reports

SYMPTOMS

All four of the men had worked with each enzyme type. None had a previous history of asthma, eczema, or hay fever. Three described work related rhinitis first occurring 18 months to 2 years after starting work in the factory (table). The fourth (patient 1) described rhinitis developing after 5 years of working with protease and 1 year with amylase. All four developed chest tightness and wheeze between 2 or 3 years later, which improved away from work. Two years after the onset of his chest symptoms, patient 1 was prescribed inhaled steroids and terbutaline which provided only partial improvement.

IMMUNOLOGICAL TESTING

None had immediate skin prick test reactions elicited by common aeroallergens (cat dander, grass pollen, andDermatophagoides pteronyssinus; Allergopharma, Reinbeck, Germany). All had immediate responses (>3 mm) to one or more enzyme solutions (1 mg/ml). Amylase provoked a response in all four, three patients (1, 3, and 4) had responses to protease, and three (1, 2, and 3) to cellulase.

With RAST and the same enzymes, we found high concentrations of circulating IgE antibodies to amylase and protease in all four men, and to cellulase in three.

BRONCHIAL PROVOCATION TESTING (figure)

Serial peak flow measurements were either not feasible or were not diagnostic in any case. We therefore undertook specific inhalation testing to make a diagnosis. Before admission the patients stopped all anti-inflammatory asthmatic treatment. Inhalation testing was carried out within 12 weeks of occupational exposure to detergent enzymes. A dust tipping method was used, with granulated enzymes (provided by the factory) crushed by hand with a pestle and mortar. With lactose as an inert control, we conducted the tests in a single blind manner. Forced expiratory volume in 1 second (FEV₁) was measured every 5–10 minutes for 1 hour after the test and subsequently for 24 hours at hourly intervals while the patient was awake. The FEV₁response to inhaled histamine was measured before and 24 hours after each test with the Cockroft method.5 Results were expressed as histamine PC_{20 .}

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Changes in baseline FEV₁ in the four patients.

None of the men reacted to the inert control but in each case the first exposure to amylase reproduced nasal symptoms similar to those experienced at work, which in the case of patient 2 was severe and occurred within 5 minutes of the test exposure. Amylase provoked an asthmatic response in all four: patients 1, 3, and 4 had a dual response; patient 2 developed an isolated late reaction, which began 6 hours after exposure. In all cases the asthmatic responses were associated with a fall in histamine PC₂₀.

Patient 1 was also tested with protease which provoked a dual asthmatic response and associated fall in his PC₂₀. Cellulase provoked an immediate nasal and mild asthmatic response but no reduction in histamine PC₂₀.

Discussion

We think that these are the first reported cases of occupational asthma in detergent manufacturers caused by allergy to bacterial amylase, demonstrated by specific inhalation testing. The cases reported are four of a large outbreak of asthma in a modern detergent factory incorporating encapsulated protease, amylase, and cellulase into detergents.

Fungal amylase, well recognised as a cause of asthma in bakers, is used as a dough improver in powdered form. Bacterial amylase derived fromBacillus Licheniformis which is immunologically distinct from fungal amylase, was used in the factory in which these men worked, encapsulated in granules.

Animal studies6 have suggested that bacterial amylase is a more potent allergen than protease, its allergenicity potentiated by concurrent inhalation of protease.7 Modern enzyme detergents often contain a mixture of enzymes, which usually include a protease and bacterial amylase. Exposure to both enzymes is likely to become increasingly common among those working in the detergent industry, increasing the risk of allergy to amylase and associated asthma in the absence of appropriate preventive measures.