Meinir Jones

An outbreak of asthma in a modern detergent factory

The striking decrease in the occurrence of protease-induced occupational asthma in the detergent Industry has been attributed to enzyme encapsulation. We report an outbreak of asthma, at least equal in size to those reported in the 1960s, in a modem European factory which has exclusively used encapsulated enzymes. A survey revealed that enzyme sensitisation and work-related respiratory symptoms were positively correlated with airborne enzyme exposure. We suggest that encapsulation alone is insufficient to prevent enzyme-Induced allergy and asthma.

Identification of the major water/salt insoluble wheat proteins involved in cereal hypersensitivity

Background Several studies have investigated water/salt soluble proteins which comprise 50% of the proteins in wheat. The remaining 50% of wheat proteins, are water/salt insoluble proteins of which there is limited information on their role in cereal hypersensitivity.

Association of HLA‐DQ5 and HLA‐DR1 with sensitization to organic acidanhydrides

Background Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten–carrier protein conjugate. Only a proportion of exposed workers develop IgE‐associated allergy to acid anhydrides.

Exposure-response in occupational allergy

Purpose of reviewThis review examines the relationship between exposure to workplace allergens and the risk of developing occupational allergy. Recent findingsEvidence suggests that the risk of developing occupational allergy increases with allergen exposure; however, with some occupational allergens, this exposure–response relationship is more complex. In laboratory animal workers, the risk of developing occupational allergy increases with exposure, except at high allergen exposure when there is a reduction in sensitization. This attenuation of specific immunoglobulin E antibody is associated with increased specific immunoglobulin G4 antibodies, which are likely to play a protective role, leading to a form of natural tolerance. Exposure–response relationships are also very dependent on the genetic susceptibility of the individual. The interaction between genes, occupational allergens and other cofactors in the environment, such as endotoxin, are also important risk factors in the development of sensitization and asthma. SummaryOccupational allergy provides a good opportunity to understand the complex relationships between exposure to allergens in the workplace, interaction with genes and the coexposures with other factors in the working environment and the increased risk of developing occupational allergy.

Human leucocyte antigen class II association in idiopathic bronchiectasis, a disease of chronic lung infection, implicates a role for adaptive immunity.

The aetiology of idiopathic bronchiectasis, a lung disease where chronic inflammation and bacterial infection leads to progressive lung damage, is unknown. A possible role for natural killer cells has been highlighted previously. However, a role for adaptive immunity is suggested by the presence of CD4 and CD8 T cells in diseased lung tissue. Evidence of a human leucocyte antigen (HLA) class II disease association would further implicate a role for adaptive immunity. To establish if there is any HLA association, we analysed HLA‐A, HLA‐B, HLA‐DQA1, HLA‐DQB1 and HLA‐DRB1 alleles in patients with idiopathic bronchiectasis and controls. Genomic DNA from 92 adults with idiopathic bronchiectasis and 101 healthy controls was analysed by polymerase chain reaction with sequence‐specific primers. We found an increase in the prevalence of HLA‐DRB1*01 DQA1*01/DQB1*05 genes in idiopathic bronchiectasis; that is, the HLA‐DR1, DQ5 haplotype (odds ratio 2·19, 95% confidence interval 1·15–4·16, P = 0·0152) compared with control subjects. The association with HLA‐DR1, DQ5 implicates a role for CD4 T cells restricted by these molecules in susceptibility to the progressive lung damage seen in this disease. This may operate either through influencing susceptibility to specific pathogens or to self‐reactivity and requires further investigation.

Pro/Con debate: Is occupational asthma induced by isocyanates an immunoglobulin E-mediated disease?

Isocyanates, low‐molecular weight chemicals essential to polyurethane production, are one of the most common causes of occupational asthma, yet the mechanisms by which exposure leads to disease remain unclear. While isocyanate asthma closely mirrors other Type I Immune Hypersensitivity (Allergic) disorders, one important characteristic of hypersensitivity (‘allergen’‐specific IgE) is reportedly absent in a large portion of affected individuals. This variation from common environmental asthma (which typically is induced by high‐molecular weight allergens) is important for two reasons. (1) Allergen‐specific IgE is an important mediator of many of the symptoms of bronchial hyper‐reactivity in ‘allergic asthma’. Lack of allergen‐specific IgE in isocyanate hypersensitive individuals suggests differences in pathogenic mechanisms, with potentially unique targets for prevention and therapy. (2) Allergen‐specific IgE forms the basis of the most commonly used diagnostic tests for hypersensitivity (skin prick and RAST). Without allergen‐specific IgE, isocyanates may go unrecognized as the cause of asthma. In hypersensitive individuals, chronic exposure can lead to bronchial hyperreactivity that persists years after exposure ceases. Thus, the question of whether or not isocyanate asthma is an IgE‐mediated disease, has important implications for disease screening/surveillance, diagnosis, treatment and prevention. The present Pro/Con Debate, addresses contemporary, controversial issues regarding IgE in isocyanate asthma.

The prognosis of occupational asthma due to detergent enzymes: clinical, immunological and employment outcomes.

Background Little is known about the prognosis of occupational asthma induced by high molecular weight proteins. Objective Our objective was to measure the clinical, immunological and employment outcomes of individuals with occupational asthma induced by detergent enzymes. Methods We undertook a workforce‐based follow‐up study in 35 (78%) of the 45 ex‐employees from a single factory with occupational asthma. In each case the diagnosis was supported by evidence of specific sensitization and characteristic changes in peak flow or a positive response to specific bronchial provocation testing. Results This group had left the factory on average 37 months before study. On review 25 (71%) reported chest symptoms during the last month. Compared with when working at the factory, most (86%) reported that their symptoms had improved. Twenty continued to attend their general practitioner for respiratory symptoms and 19 still used asthma medications. Since leaving the factory 16 (46%) and four (11%) had found full‐time or part‐time employment, respectively; of these 16 found they were paid less than when they worked at the factory. The remaining 15 subjects had not had any paid employment. All but two had positive skin prick tests to one or more three detergent enzymes. The estimated half‐life of serum‐specific IgE antibodies was 20 months for protease, and 21 months for cellulase and amylase. Conclusions Population‐based follow‐up studies of the prognosis of occupational asthma are rare but probably avoid the bias in clinic‐derived surveys. This study demonstrates that 3 years after the avoidance of exposure with detergent enzymes most patients continue to be troubled by, albeit improved, symptoms and experience difficulty in re‐employment.

Determination of the T cell epitopes of the lipocalin allergen, Rat n 1

Background Laboratory animal allergy (LAA) is an important cause of occupational sensitization and asthma. Rats are a frequent cause of LAA and the major rat allergen, Rat n 1, is a member of the lipocalin protein family, which includes several other animal allergens such as the cow allergen, Bos d 2. To date, Bos d 2 is the only mammalian lipocalin allergen to have been studied in detail.

Domestic aeroallergen levels in Barcelona and Menorca (Spain)

Exposure to common indoor allergens is known to be associated with sensitization and triggers of asthma. Levels of allergens have been barely described in Mediterranean countries. This study reports domestic allergen levels among the general population of two regions of Spain. Dust samples were collected from living rooms and mattresses in homes of infants in Barcelona (n = 366) and Menorca (n = 475) and assayed for house dust mite (Der p 1) and cat allergen (Fel d 1) concentrations by enzyme‐linked immunoabsorbent assay (ELISA). Geometric mean values (95% CI) of Der p 1 were 0.77 µg/g (0.65, 0.92) in living rooms and 0.68 (0.56, 0.82) in childrens mattresses in Barcelona, and 9.06 (7.93–10.34) and 3.12 (2.71–3.59) in Menorca, respectively. Fel d 1 levels were 0.37 µg/g (0.31, 0.45) and 0.14 (0.12, 0.18) in Barcelona, and 0.42 (0.35, 0.50) and 0.20 (0.18, 0.24) in Menorca. Home characteristics were not consistently related to levels of aeroallergens in either location. Differences in Der p 1 levels in the two locations indicate that levels cannot be extrapolated from one part of a country to another with any certainty. Additionally, allergen reduction measures related to indoor sources must be specific to each location.

Occupational asthma caused by bacillary amylase used in the detergent industry.

Four cases are reported of occupational asthma due to amylase derived from Bacillus licheniformis, used in detergent washing powders. It is thought that these are the first reported cases of asthma due to this enzyme in the detergent industry. All four employees (men) were from the same factory and none had a history of asthma or atopy. All developed symptoms of wheeze at work after an initial symptom free period. Symptoms improved during periods away from work. All undertook serial peak flow recordings (not diagnostic) and underwent skin prick tests, radio allergosorbent test (RAST) measurement, and specific bronchial provocation testing. The bronchial provocation testing was performed by a dust tipping method in a single blind manner, with lactose as an inert control and powdered amylase, provided by the employer, as an active agent. Serial measurements of forced expiratory volume in 1 second (FEV1) were recorded and histamine provocative concentration causing a 20% fall in FEV1 (PC20) tests were determined before and 24 hours after each challenge. Patient 1 developed an isolated early reaction, patient 2 an isolated late reaction, and patients 3 and 4 developed dual reactions. All showed an increased non-specific bronchial responsiveness after active challenge. The introduction of encapsulated enzymes in the detergent industry was followed by a reduction in the incidence of respiratory sensitisation. These patients developed occupational asthma despite working only with encapsulated enzymes. This highlights the importance of careful surveillance after the introduction of new agents in the workplace.