Epidemiology

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Occupational asthma is the most frequently reported occupational respiratory disorder in westernised industrialised populations (Kor 2001, McDonald 2000, Provencher 1997). In countries such as South Africa and the Czech Republic, where mining is common, occupational asthma is the second most prevalent occupational respiratory disorder after pneumoconiosis (Brehl 2003, Hnizdo 2001).

What is the frequency of occupational asthma?

There are no complete registries for reporting occupational diseases such as occupational asthma and the true frequency of the disease is not known. Underreporting is likely and reports may not differentiate between the various types of work-related asthma. Published frequencies come from surveillance schemes, compensation registries or from epidemiological studies of the relationship between asthma and occupation. The incidence of occupationally associated asthma varies between countries depending on the methodology of data collection, definition of cases and the predominant work sectors and occupations. A systematic review of 43 risk estimates from 19 countries demonstrated an attributable risk of 9% whilst the 12 highest scoring studies demonstrated an attributable risk of 15% (Blanc 1999). Another review of 21 studies similarly demonstrated an attributable risk of 15% (Balmes 2003).

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Occupational factors are estimated to account for 9-15% of cases of asthma in adults of working age, including new onset or recurrent disease.

( Balmes 2003, Blanc 1999)

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The annual population incidence of occupationally related asthma ranges from an estimated 12 to 170 cases per million workers with an estimated mean of 47 cases per million workers.

( Ameille 2003, Blanc 1999, Karjalainen 2000, Meredith 1991)

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The population incidence of occupational asthma may be underestimated by as much as 50%.

( deBono 1999)

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The reported incidence of occupational asthma has not decreased in recent years.

( Cortona 2001, Meyer 2001, Reijula 1996)

Which agents cause occupational asthma and which workers are at risk?

Several hundred agents have been reported to cause occupational asthma and new causes are reported regularly in the medical literature. The predominant causative agents and the jobs most commonly reported to incur high risk reflect variations of economic activity both between and within different countries, methods of data collection - surveillance schemes and population studies - occupational classifications of workers and different perceptions of whether asthma is occupational or not.

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The most frequently reported agents include isocyanates, flour and grain dust, colophony and fluxes, latex, animals, aldehydes and wood dust.

( Ameille 2003, Brhel 2003, Cortona 2001, Gannon 1993, McDonald 2000, Meredith 1991, Meyer 1999, Sallie 1994, Toren 1999)

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The workers most commonly reported to surveillance schemes of occupational asthma include paint sprayers, bakers and pastry makers, nurses, chemical workers, animal handlers, welders, food processing workers and timber workers.

( Ameille 2003, Brhel 2003, Gannon 1993, Karjalainen 2002, McDonald 2000, Meredith 1991, Meyer 1999, Reijula 1996, Sallie 1994, Toren 1999)

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The workers reported from population studies to be at increased risk of developing asthma include bakers, food processors, forestry workers, chemical workers, plastics and rubber workers, metal workers, welders, textile workers, electrical and electronic production workers, storage workers, farm workers, waiters, cleaners, painters, plastic workers, dental workers and laboratory technicians.

( Jaakkola 2003, Johnson 2000, Kogevinas 1996, Kogevinas 1999)

What are the risk factors for developing occupational asthma?

Most studies of risk factors for occupational asthma are of cross-sectional design. Where a disease is clearly attributable to exposures at work it is likely to result in differential assortment of employees with or without disease both within and out of an occupation or workplace. Cross-sectional analyses of a current workforce may reflect the resulting survivor effects; moreover they are generally incapable of distinguishing cause from effect. As a result, the absence of any perceptible effect of a putative risk factor may be a consequence more of study design, than of reality. There are few published studies of more robust cohort or case-referent study design. Furthermore there is likely to be considerable publication bias in this area. However, four risk factors have been identified for a number of agents including the predisposing factors of atopy and genetic predisposition, the causative factor of exposure to an agent at work and the contributing factor of cigarette smoking.

Is exposure to agents in the workplace a risk factor for developing occupational asthma?

A direct relationship between occupational asthma and allergen exposure at work has been demonstrated with acid anhydrides (Grammer 1994, Liss 1993), cimetidine (Coutts 1984), colophony (Burge 1981), enzymes (Cathcart 1997, Cullinan 2000, Juniper 1997, Vanhanen 1997, Weill 1971), green coffee and castor bean (Osterman 1982), flour allergens (Brisman 2000, Cullinan 1994, Cullinan 2001 Heederik 2001, Houba 1998, Musk 1989), crab (Ortega 2001), isocyanates (Meredith 2000, Petsonk 2000, Tarlo 1997a), laboratory animal allergens (Cullinan 1999, Kruize 1997, Platts-Mills 1987), piperazine (Hagmar 1984), platinum salts (Calverley 1995), prawns (McSharry 1994) and western red cedar (Brooks 1981). Most of these studies have also demonstrated a positive exposure-response relationship for sensitisation. Studies limited to sensitisation, rather than asthma, have demonstrated a relationship with exposure to acid anhydrides (Nielsen 2001), bakery enzymes (Houba 1996, Nieuwenhuijsen 1999, Vanhanen 1997), laboratory animals (Heederik 1999) and platinum salts (Merget 2000).

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The risk of sensitisation and occupational asthma is increased by higher exposures to many workplace agents.

( Brisman 2000, Brooks 1981, Calverley 1995, Cathcart 1997, Coutts 1984, Cullinan 1994, Cullinan 1999, Cullinan 2000, Cullinan 2001, Grammer 1994, Hagmar 1984, Heederik 2001, Hnizdo 2001, Juniper 1977, Kruize 1997, Liss 1993, McSharry 1994, Meredith 1991, Musk 1989, Ortega 2001, Osterman 1982, PlattsMills 1987, Tarlo 1997, Vanhanen 1997, Weill 1971)

Is atopy a risk factor for developing occupational asthma?

Atopy is a state characterised by the propensity to produce specific immunoglobulin IgE on ordinary exposure to common allergens in the subject's environment. Differences between studies relating to the ascertainment of atopy range from those that use an immunological test such as skin prick testing to those that rely on a personal or family history of allergic disease i.e., asthma, eczema or hayfever. This can cause inconsistencies between reported observations. Atopy has been reported to increase the risk of occupational asthma in workers exposed to detergent enzymes (Juniper 1984, Weill 1971, Zentner 1997), isocyanates (Meredith 2000, Ucgun 1998) laboratory and other animals (Agrup 1986, Botham 1987, Cockcroft 1981, Cullinan 1999, Gautrin 2001a, Gautrin 2001b, Jeal 2003, Sjostedt 1989, Sjostedt 1993, Krakowiak 2002, Kruize 1997, Platts-Mills 1987, Venables 1988a), bakery allergens (Baur 1998a, De Zotti 1997, De Zotti 2000, Droste 2003, Houba 1998, Talini 2002) and some reactive dyes (Docker 1987). Other studies have demonstrated no such association between atopy and occupational asthma due to exposure to cork (Winck 2004), isocyanates (Butcher 1977, Cullen 1996, Petsonk 2000), detergent enzymes (Cullinan 2000), glutaraldehyde (Di Stefano 1999), salmon (Douglas 1995), crab (Cartier 1984), hexahydrophthalic anhydride (Grammer 1996), platinum salts (Merget 2000, Venables 1989a) and plicatic acid in western red cedar (Chang-Yeung 1982). As with exposure, some studies that examined asthma also examined, where possible, specific sensitisation. Atopy has been associated with an increased risk of sensitisation in workers exposed to various enzymes (Cullinan 2001, Flood 1985, Greenberg 1970, Houba 1996, Juniper 1977, Newhouse 1970, Vanhanen 1997, Witmeur 1973, Zentner 1997), green coffee and castor bean (Osterman 1982, Romano 1995), bakery allergens (Baur 1998a, Cullinan 2001, De Zotti 1994, De Zotti 1997, Houba 1998, Heederik 2001, Prichard 1984), laboratory animals (Cullinan 1999), crab (Cartier 1984), prawn (McSharry 1994) and acid anhyrides (Venables 1985a, Nielsen 2001).

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Atopy increases the risk of developing occupational asthma caused by exposure to many high molecular weight agents that induce the production of specific IgE antibodies.

( Agrup 1986, Baur 1998, Botham 1987, Cullinan 1999, DeZotti 1997, DeZotti 2000, Droste 2003, Gautrin 2001, Gautrin 2001, Jeal 2003, Juniper 1984, Krakowiak 2002, Kruize 1997, PlattsMills 1987, Sjostedt 1989, Sjostedt 1993, Talini 2002, Venables 1988, Weill 1971, Zentner 1997)

Is there a genetic predisposition for developing occupational asthma?

That only a proportion of workers develop occupational asthma despite similar exposures, suggests an underlying genetic susceptibility to occupational asthma. A number of studies have examined the role of genes coding for Class I or II human leukocyte antigen (HLA) and respiratory anti-oxidant expression in occupational asthma attributed to isocyanates (Balboni 1996, Beghe 2004, Bernstein 1997, Bignon 1994, Mapp 2000, Mapp 2002, Piirila 2001, Rihs 1997), complex platinum salts (Newman Taylor 1999), western red cedar (Horne 2000), acid anhydrides (Young 1995) and laboratory animal proteins (Sjostedt 1996, Jeal 2003). Most studies were based on small sample sizes and the findings are either inconsistent or unreplicated.

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Genetic polymorphisms that code for human leukocyte antigen class II genes or respiratory anti-oxidant mechanisms may predispose to occupational asthma for a number of agents.

( Balboni 1996, Bignon 1994, Horne 2000, Jeal 2003, Mapp 2002, Mapp 2000)

Is smoking a risk factor for developing occupational asthma?

Smoking has been identified to increase the risk of occupational asthma in workers exposed to: isocyanates (Cullen 1996, Meredith 2000, Ucgun 1998), platinum salts (Calverley 1995, Venables 1989a), salmon (Douglas 1995) and snow crab (Cartier 1984). One study demonstrated a dose-dependent effect (Venables 1989a). Smoking has been identified to increase the risk of sensitisation in only a few studies with exposure to green coffee and castor bean (Osterman 1982, Romano 1995), platinum salts (Baker 1990, Merget 2000, Niezborala 1996), prawn (McSharry1994), flour (De Zotti 1994). The role of cigarette smoking is unclear for asthma due to exposure to acid anhydrides, enzymes and laboratory animals. Some studies have shown an increased risk of laboratory animal asthma in smokers (Cullinan 1999, Krakowiak 1997, Venables 1988a), whereas others have shown no effect (Agrup 1986, Gautrin 2001a, Gautrin 2001b, Kruize 1997, Meijer 2002). For exposure to acid anhydrides, studies have demonstrated both negative (Grammer 1996, Liss 1993) and positive (Venables 1985a) correlation with specific IgE. Similar conflicting evidence is available for detergent enzymes (Johnsen 1997, Weill 1971). Whilst one study demonstrated an increased risk of sensitisation in bakery workers (DeZotti 1994), smoking does not appear to increase the risk of asthma in bakery workers (Baur 1998a, Cullinan 2001, De Zotti 1994, Houba 1998).

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Cigarette smoking can increase the risk of developing occupational asthma with some sensitising agents.

( Calverley 1995, Cartier 1984, Cullen 1996, Douglas 1995, Meredith 1991, Niezborala 1996, Venables 1989)

Is occupational rhinitis a risk factor for developing occupational asthma?

Rhinitis and asthma frequently occur together. There is epidemiological evidence from the general population of a strong association between the development of asthma and a previous history of either allergic or perennial rhinitis. Occupational rhinitis is purported to be a risk factor for the development of occupational asthma, especially for high-molecular-weight sensitisers. One population study reported that occupational rhinitis (defined as work-related symptoms, specific sensitisation to a work substance, positive nasal challenge and exclusion of other causes) carried a crude relative risk of asthma of 4.8 (Karjalainen 2003). The relative risk was highest among farmers and wood workers and the greatest risk of asthma was in the year after rhinitis was reported. Rates of co-morbid rhinitis or rhino-conjunctivitis of between 45% and 90% have been reported in subjects suffering from IgE associated occupational asthma attributed to acid anhydrides (Grammer 2002a, Wernfors 1986), laboratory animals (Cullinan 1999, Gautrin 2001a, Gautrin 2001b), snow crab (Cartier 1984) and wheat flour (Houba 1998). The intensity of nasal symptoms appears to be significantly more pronounced in the case of HMW agents (Malo 1997).

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Occupational rhinitis and occupational asthma frequently occur as co-morbid conditions in IgE associated occupational asthma.

( Cartier 1984, Cortona 2001, Cullinan 1999, Gautrin 2001, Gautrin 2001, Grammer 2002, Houba 1998, Malo 1997, Wernfors 1986)

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Rhino-conjunctivitis is more likely to appear before the onset of IgE associated occupational asthma.

( Cortona 2001, Cullinan 1999, Gautrin 2001, Gautrin 2001, Grammer 2002, Karjalainen 2003, Malo 1997)

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The risk of developing occupational asthma is highest in the year after the onset of occupational rhinitis.

( Cortona 2001, Karjalainen 2003)

When are symptoms of occupational asthma most likely to develop?

The latent interval between first exposure and the onset of recognisable symptoms can vary depending on the agent, the management of exposure and biological variability. Whilst the latent interval can extend to many years (Bar-Sela 1984, Cortona 2001, Kim 1999, Munoz 2003), the risk of occupational asthma appears to be highest soon after first exposure to laboratory animal allergens (Agrup 1986, Cullinan 1999, Gautrin 2001a, Gautrin 2001b, Krakowiak 1997, Platts-Mills 1987), isocyanates (Venables 1985b), platinum salts (Calverley 1995, Niezborala 1996, Venables 1989a and azodicarbonamide (Slovak 1981).

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Sensitisation and occupational asthma are most likely to develop in the first years of exposure for workers exposed to enzymes, complex platinum salts, isocyanates and laboratory animal allergens.

( Agrup 1986, Calverley 1995, Cullinan 1999, Gautrin 2001, Gautrin 2001, Johnsen 1997, Krakowiak 1997, Niezborala 1996, PlattsMills 1987, Slovak 1981, Venables 1989)