All About Allergens

From the World Health Organization in its report WHO Guidelines for Indoor Air Quality: Dampness and Mould, published July 16, 2009

Allergens

All agents that can induce specific immune responses (resulting in the production of specific antibodies) are also potential allergens. The term allergen can refer to a single molecule, a mixture of molecules or a particle from which allergen molecules can be eluted. The latter can be dead material, like mite faecal particles, or viable propagules, such as bacteria or mould spores. Thus, allergens comprise a large variety of macromolecular structures, ranging from low-relative-molecular-mass sensitizers (mainly chemicals such as formaldehyde) to high-relativemolecular-mass sensitizers (such as polymeric carbohydrates and proteins).

In damp indoor environments, those with a high relative molecular mass are most relevant, in particular house dust mite allergens and fungal allergens.

House dust mite allergens

Dust mites produce the predominant inhalation allergens in many parts of the world. The most common mite species that produce allergens are Dermatophagoides pteronyssinus and Dermatophagoides farinae. The major allergens produced by D. pteronyssisus (called Der p I and Der p II) are proteases, which are present in large amounts in faecal pellets (Institute of Medicine, 2000). The major allergen produced by D. farinae is Der f I. Elevated levels of these allergens have been detected in house dust, mattress dust and bedding in damp houses (van Strien et al., 1994; Simpson et al., 2002; van Strien et al., 2004). As the focus of these guidelines is indoor dampness and microorganisms, dust mite allergen levels are not discussed further.

Fungal allergens

Many fungal species produce type I allergens, and immunoglobulin (Ig)E sensitization to the commonest outdoor and indoor fungal species, like Alternaria, Penicillium, Aspergillus and Cladosporium spp., is strongly associated with allergic respiratory disease, especially asthma. Fungi are also well-known sources of type III (or IgG-inducing) allergens. The species involved include many common genera such as Penicillium and Aspergillus, which can be found in most houses. At high concentrations, fungi may also be involved in combined type III and IV allergic reactions, including hypersensitivity pneumonitis.

Many fungal allergens are glycopeptides with enzymatic properties. They are found in spores, hyphae and fungal fragments but are released in greater amounts during germination and mycelial growth, which may occur inside the airways (Green et al., 2006).

The viability of spores is therefore important for allergenic expression, as confirmed in some studies in experimental animals. Although non-viable fungal spores and hyphae release allergens at lower concentrations, they are still likely to play an important role in fungi-related allergies and respiratory effects. Non-viable fungal spores and fungal fragments also contain potentially harmful compounds such as (1→3)-β-D-glucans and mycotoxins. Species of the genera Cladosporium, Alternaria and Aspergillus have been shown to produce a variety of allergens, including several major ones: Cla h I (Cladosporum herbarum), Alt a I and Alt a II (Alternaria alternata) and Asp f I and Asp f III (Aspergillus fumigatus). Nonetheless, the most potent allergenic proteins, identified as major allergens in fungal extracts produced in vitro, might not be the same as those to which people are actually exposed in indoor environments. This might explain the negative skin-prick test and IgE results in people with asthma.

Commercial assays are available for only a limited number of indoor fungal allergens (including Alternaria allergens, see section 2.4.3) because of difficulties in the manufacture and standardization of fungal allergen extracts. Therefore, little information is available on exposure to these allergens.

Many fungi and some yeast replicate by producing numerous spores that are well adapted to airborne dispersal. Spores are typically 2–10 μm in length. They can stay airborne for long periods and may deposit in the respiratory system, some smaller spores reaching the alveoli (Eduard, 2006). Fungi also release even smaller fungal fragments (Gorny, 2004), which are derived from broken or fractured spores and hyphae and can be categorized into submicron particles (< 1 μm) or larger fungal fragments (> 1 μm). Even more fungal fragments than spores may be deposited in the respiratory tract (Cho et al., 2005); like spores, they are known to contain allergens (Green et al., 2006) and mycotoxins (Brasel et al., 2005a). Both spores and fungal fragments may therefore be involved in mould-related adverse health effects.

The aerosolization of fungal matter and its subsequent inhalation are only partly understood, but two mechanisms are believed to be of particular importance:

Release of spores or fungal fragments by active discharge, indoor air movement or physical disturbance caused by people or pets; and (2) resuspension of settled fungal matter due to human activities. Factors that may affect the rate of release of spores or fungal fragments include air velocity, time, colony structure, desiccation stress, moisture condition and vibration. These factors may affect the rate of aerosolization of spores and fungal fragments differently (Gorny, 2004).

Fungal spores are ubiquitous in outdoor air, the levels ranging from less than 100 to more than 105 spores/m3. The indoor levels are usually lower than those outdoors but may be increased by unintended fungal growth in damp buildings (Flannigan, Samson, Miller, 2001). Studies in damp indoor environments have shown a wide diversity of fungal species and genera, probably due to differences in climate, indoor temperature and humidity, and building materials, as well as differences in sample collection and subsequent culture.

Fungi are often found on wet window frames and damp walls of bedrooms, living rooms and kitchens. Mattresses constitute an important reservoir for mould, with measured concentrations of 103–107 spores/g of dust (Verhoeff et al., 1994a). Several extensive reviews on fungal species found in damp indoor environments have been published (e.g. Flannigan, Samson, Miller, 2001).

The airborne concentrations of viable fungi in indoor environments are usually in the order of a few to several thousand colony-forming units (CFUs) per cubic metre of air. In a given space, concentrations of fungi are highly variable and depend on such factors as: climate and season, type of fungus, construction, age and use of the building, and ventilation rate. They also depend largely on the sampling and analytical methods used, making valid comparisons between studies difficult.

Indoor fungal fragments are not commonly measured in field studies, but a study with an aerosolization chamber showed that submicron fungal fragments from culture plates and mould-contaminated ceiling tiles aerosolized simultaneously with spores but at substantially higher concentrations (320–514 times higher) (Gorny et al., 2002; Cho et al., 2005). This suggests that indoor exposure to fungal fragments is at least as important as exposure to fungal spores.