Effects Of Indoor Air Quality On Health Biology Essay

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The effects of indoor air quality on health have been an area of increasing concern and scientific interest over the last 30 years. However Outdoor air quality is a more publicised concern due to the issues linking it to the burning of fossil fuels and vehicle emissions. Nonetheless surveys show that people in industrialised nations on average spend between 85-92% of their time indoors and only 2-9% of their time outdoors (Klepies et al 2001), this therefore demonstrates the importance of indoor air quality and the understanding of the health impacts that arise when it is not maintained. One of the most frequently encountered health effects associated with poor indoor air quality is Sick building syndrome (SBS). The United States Environmental Protection Agency (1991) describes SBS as the term used to describe situations in which building occupants experience acute health and comfort effects that appear to be linked to time spent in a building, but no specific illness or cause can be identified. In contrast to this, the term building related illness (BRI) can be used when symptoms of diagnosable illness are identified and can be attributed directly to airborne building contaminants. Indoor air contaminants can be both biotic and abiotic, and to a large extent, the increase in the occurrence of SBS and BRI is due to the changes of modern building design, which have been driven by rising fuel costs since the 1970s. The requirement for increased energy efficiency of buildings, this has resulted in buildings with much better insulation, and as a result, much less ventilation (Jones, 1999). In conjunction with this there has been an increase in the use of synthetic materials for use within building construction and these can often act as a source for airborne contaminants. These materials can include paints, solvents and wood preservatives (Jones, 1999).Table 1 outlines major indoor pollutants and their emission sources.


paints, tobacco smoke

Polycyclic aromatic hydrocarbons, Fuel combustion, tobacco smoke

This paper is primarily focused on the biotic airborne contaminants present within indoor environments, and biological airborne contaminants, often referred to as bio aerosols. These are a significant factor in indoor air pollution, and contribute to approximately 5-35% of indoor air pollution (Fung and Hughson, 2003) (Srikanth et a.,l 2008).

In recent years microorganisms have been the primary source of indoor air contamination in as many as 35-50% of indoor air quality cases (McNeel and Kreutzer, 1996). Biological air contaminants are also an area of great concern due to the threat of the utilisation of pathogenic microorganisms or microbial toxins as weapons of mass destruction (Stetzenbach et al., 2004). Bio aerosols consist of bacterial and fungal cells, cellular fragments, fungal spores, pollen, viruses and by-products of microbial metabolism which may be present as particulate or liquid, as well as microbial volatile organic compounds (mVOCS) (Hardin et al., 2003). Exposure to indoor bio-contaminants can be by inhalation, ingestion and dermal contact, however the major route of human exposure to airborne biological contaminants is by inhalation (Srikanth et al., 2008). Table 2 shows some of the most common building related diseases and syndromes and examples of causative organisms.

Disease/Syndrome Examples of causal organisms cited

Serpula (dry rot)

Trichosporon, Serpula, Penicillium, Bacillus

Fungi as indoor airborne contaminants

Fungi are an important factor when considering airborne contaminants due to their ubiquitous nature in both indoor and outdoor environments (Terr, 2009).

Fungi may be transported into buildings on the surface of new materials or on clothing, as well as penetrating buildings through active or passive ventilation. As a result fungi are found in the dust and surfaces within every building, including those with no problems with damp or water damage (WHO, 2009).

Fungi cause a variety of negative health effects and this can occur through three mechanisms of pathogenicity, infection, allergy and toxicity (Terr, 2009).

There has been a massive increase in media and public awareness about the presence and health effects of mould in indoor environments, and this has been largely driven by headlines and high profile cases of litigation about toxic moulds (Robbins et a.,l 2000). Fungi are a major contributor to biological indoor airborne contamination as they are very adaptable and can colonize dead and decaying organic matter such as textiles, leather, wood, paper, and even damp inorganic material such as glass, painted surfaces or bare concrete if organic nutrients such as dust or soil particles are available (McNeel and Kreutzer, 1996). Fungi contaminate the indoor environment as fungal spores, mycelial fragments and mycotoxins (Stetzenbach et al., 2004). The presence of excess water promotes fungal growth, allowing for the growth on building materials within buildings, and in the UK, the prevalence of damp and mouldy homes has been reported to be 17 to 46% (Martin et al., 1987; Platt et al., 1989; Gorni et al., 2002).In North America, cross-sectional questionnaire studies have found that 27 to 36% of homes have mould problems (Dales et al., 1991). Studies that included indoor air quality measurements have shown even higher numbers, from 42 to 56% (Crandall and Sieber, 1996; Ellringer et al., 2000).

In general fungi are not largely harmful to humans beyond common superficial infections, and invasive fungal infection that can lead to fatality rarely occurs in immunocompetent individuals and is limited to only a few fungal species viz. Blastomyces, Coccidioides, Cryptococcus, and Histoplasma (ACOEM, 2002). However in immunocompromised individuals fungal infections in which there is deep tissue invasion, are a much greater area of risk. The risk of serious fungal infection is greatest when the patients are immune compromised and as a result great care needs to be taken within hospital environments to understand and monitor biological airborne contaminants, and to ensure measures are taken to avoid fungal, bacterial, and viral infection (ACOEM, 2002).

When considering indoor air quality there are a number of fungi that are commonly found contaminating indoor air that are associated with negative health effects through SBS and BRI, the most common are Penicillium, Aspergillus, Cladosporium, Trichoderma and Stachybotrys spp. (Jones, 1999; ACOEM, 2002; Terr 2009). Of these in terms of indoor building contaminants, much attention has focussed on Aspergillus spp. and Stachybortys spp.

Aspergillus is a particularly important contaminant of indoor air due to the wide range of negative health effects it can cause, these are collectively termed aspergillosis, the most important forms of aspergillosis are Allergic bronchopulmonary aspergillosis (ABPA), Allergic fungal sinusitis, acute invasive aspergillosis and formation of aspergillomas. The most important clinical species are A. fumigatus, A. flavus, A. terreus and A. niger (Klich, 2009).

The levels of airborne fungi encountered in indoor environments will generally be a reflection of outdoor sources. Indoor levels are usually between 40% to 80% of outdoor levels, except when outdoor levels are low. However, a number of indoor activities and materials can also contribute to indoor mould sources, such as plants, pets, and moulds brought in on footwear and clothing. Contaminated air conditioners and humidifiers can also harbour and circulate indoor spores and their allergens (Reynolds et al., 1990; Chapman et al., 2003).

Allergic effects of airborne fungi


Table 3. Genera of fungi frequently associated with allergy from Kurup (2000).

Allergic asthma or allergic rhinitis is triggered by breathing in mould spores or hyphal fragments. Residential or occupational fungal exposures may be a considerable factor in an individuals allergic airway disease depending on the subjects profile of allergic sensitivity and the levels of indoor exposures (Hardin et al., 2003). Individuals with this type of mould allergy are atopic individuals, that is, have allergic asthma, allergic rhinitis, or atopic dermatitis and manifest allergic (IgE) antibodies to a wide range of environmental proteins among which moulds are only one participant. These individuals generally will have allergic reactivity against other important indoor and outdoor allergens such as animal dander, dust mites, and weed, tree, and grass pollens.

Among the fungi, the most important indoor allergenic moulds are Penicillium and Aspergillus spp. (Bush et al., 2006). Outdoor moulds, for example, Cladosporium and Alternaria, as well as pollens, can often be found at high levels indoors if there is access for outdoor air (for example open windows; Hardin et al., 2003). About 40% of the population are atopic and express high levels of allergic antibodies to inhalant allergens. Of these 25%, or 10% of the population, have allergic antibodies to common inhalant moulds (Horner et al., 1995). Because about half of persons with allergic antibodies will express clinical disease from those antibodies, about 5% of the population is predicted to have, at some time, allergic symptoms from moulds (Hardin et al,. 2003).

Although indoor moulds are well-recognized allergens, outdoor moulds are more generally important. A growing body of literature associates a variety of diagnosable respiratory illnesses (asthma, wheezing, cough, and phlegm), particularly in children, with residence in damp or water-damaged homes. Several studies have demonstrated that there are increased inflammatory mediators in the nasal fluids of persons in damp buildings, but also found that mould spores themselves were not responsible for these changes (Purokivi et al., 2001; Roponen et al., 2002). Also, despite the fact that mould spores act as a causative agent for asthma in specifically sensitised patients has been widely accepted for many years within medicine, there have been studies in which deliberate inhalation exposure to massive quantities of Penicillium chrysogenum spores have failed to induce an allergic response in sensitised individuals (Meyer at al., 2005).

Hypersensitivity pneumonitis (HP) results from exaggeration of the normal IgG immune response against inhaled foreign proteins and is characterized by very high serum levels of specific IgG antibodies. These are classically detected in precipitin tests performed as double diffusion tests and also characterised by inhalation exposure to very large quantities of fungal proteins (Petal et al., 2001). The resulting interaction between the inhaled fungal proteins and fungal directed cell-mediated and humoral (antibody) immune reactivity leads to an intense local immune reaction recognized as Hypersensitivity pneumonitis. The disease exists in 3 overlapping stages with characteristic pathologic features (Chapman et al., 2003).

The acute stage features a mononuclear cell pneumonitis and is the most common clinical presentation.

HP typically starts with influenza-like symptoms 4 to 8 hours after exposure to the inciting antigen. Specific symptoms include a non-productive cough, dyspnea, fever, chills, myalgias, and malaise. The symptoms typically peak in intensity between 12 and 24 hours following exposure and improve without specific treatment within 48 hours after removal of the source of exposure. The episodes of symptoms recur, with increasing intensity, whenever the inciting antigen is inhaled. On physical examination the patient is ill-appearing with tachypnea, tachycardia, and bibasilar inspiratory rales. Respiratory failure may occur in severely ill individuals with significant hypoxemia (Lacasse et al., 2003; Mohr, 2004). Laboratory studies have shown that during acute episodes typically there are elevated neutrophil granulocyte levels and occasional lymphopenia, as well as normal IgE levels in peripheral blood. Rheumatoid factor is positive in 50% of patients and nonspecific markers of inflammation, such as erythrocyte sedimentation rate and C-reactive protein, are frequently elevated. Serum precipitating antibodies to the inciting organic antigen, which are usually IgG, but may be IgM or IgA, can be demonstrated in most patients (Mohr, 2004).

Some patients develop a sub acute form of HP as a result of repeated exposure to low doses of the inciting organic antigen. The sub acute phase is characterized by an interstitial granulomatous inflammation, exertional dyspnea, fatigue, and occasional cough. Fever or a low-grade increase in temperature may occur. Symptoms of the sub acute form typically improve without treatment within 24 hours after cessation of exposure; however they tend to recur shortly after re-exposure to a low dose of the inciting antigen. Therefore, individuals who have frequent, recurrent exposure to an inciting antigen may experience numerous repeated exacerbations and remissions of sub acute HP over an extended period of time (Mohr, 2004).

Approximately 5% of patients with HP develop the chronic form of the disease (Salvaggio, 1994). Chronic HP is characterized by the development of pulmonary fibrosis. It develops gradually over a period of months to years in susceptible individuals who encounter frequent or continuous exposure to the inciting antigen. Recurrent episodes of sub acute HP often result in the development of chronic disease. Chronic HP may be progressive and irreversible, especially with continued exposure to the inciting antigen. With chronic HP the reported mortality rates are in the range of 1 to 10% (Braun et al., 1979; Kokkarinen et al., 1994). Symptoms of chronic HP resemble those of chronic bronchitis, including progressive cough, mucus production, and dyspnea on exertion, weight loss, anorexia, and malaise (Mohr,2004).

As opposed to immediate hypersensitivity reactions to mould proteins, HP is not induced by normal or even relatively elevated levels of mould spores. Most cases of HP result from occupational exposures, although cases have also been attributed to pet birds, humidifiers, and heating, ventilating, and air conditioning systems (Kurup et al., 2005). The predominant organisms in the ventilating and air conditioning system exposures are thermophilic Actinomyces, which are not moulds but rather are filamentous bacteria that can grow at high temperatures (Hardin et al., 2003). The presence of high levels of a specific antibody, generally demonstrated as the presence of precipitating antibodies, is required to initiate HP but is not diagnostic of HP (Rodrigo et al., 2000). More than half of the people who have occupational exposure to high levels of a specific protein have such precipitin antibodies but do not have clinical disease (Hardin et al., 2003).

The uncommon Allergic Syndromes such as Allergic Bronchopulmonary aspergillosis (ABPA) and Allergic fungal sinusitis (AFS) are conditions that are unusual variants of allergic (IgE-mediated) reactions in which fungi actually grow within the patients airway (Leblonde and Tonnel, 2005). ABPA is the classic form of these uncommon syndromes, and it mainly occurs in allergic individuals who generally have airway damage from previous illnesses leading to bronchial damage or irregularities impairing normal drainage. One such disease that can increase susceptibility to ABPA is bronchiectasis (Cockrill and Hales, 1999). The important element with respect to the health effect in ABPA is the underlying anatomic change in the lung and a non specific mould exposure because at-risk individuals will have ongoing exposures caused by the ubiquitous nature of the fungi involved (Bush et al., 2006).

Bronchial disease and old cavitary lung disease are predisposing factors which contribute to fungal colonization and the formation of mycetomas. Aspergillus may colonize these areas without invading adjacent tissues. This type of fungal colonization is without adverse health consequence unless the subject is allergic to the specific invading fungus, in which case there may be ongoing allergic reactivity to fungal proteins released directly into the body (Hardin et al., 2003).

Toxicity of airborne fungi

Toxicity in mould and other fungi arises through the production and action of mycotoxins.

Mycotoxins are diverse secondary metabolites produced by fungi growing on a variety of substrates, and these can be foodstuffs consumed by both animals and humans (Corrier, 1991; Kuhn and Ghannoum, 2003). Table 4 shows the mycotoxins that are produced and some of the most common fungal species that produce them. Synthesis of mycotoxins by moulds is variable, unpredictable and to a large extent dependent upon the substrate, either in nature or on laboratory media. Mycotoxins can be found in all forms of the various mould structures including hyphae, spores, they can also be released from fungal structures and contained within environmental dust (Terr, 2009). Clinical toxicological syndromes caused by ingestion of large amounts of mycotoxins have been well documented and characterized in animals, they range from acute mortality to slow growth and reduced reproductive efficiency (Kuhn and Ghannoum, 2003). The effects of mycotoxins on humans are much less well characterized (Corrier, 1991).

Outbreaks of various forms of animal mycotoxicosis have occurred worldwide in livestock, these include sweet clover poisoning, mouldy-corn toxicosis, cornstalk disease, bovine hyperkeratosis, and poultry hemorrhagic syndrome (Bennett and Klich, 2003).

Mycotoxins are most likely responsible for a range of acute and chronic health effects that cannot be directly attributed to fungal growth within the host or allergic reactions to foreign proteins (Pitt, 1994). There are at least 21 different mycotoxin classes, with over 400 individual toxins produced by at least 350 fungi (Kuhn and Ghannoum, 2003). They are all complex organic compounds of 200 to 800 kD and are not volatile at ambient temperatures. A number of these are plant disease virulence factors, while others kill other fungi and microorganisms and thus may represent spillover effects when causing disease in animals (Peraica et al., 1999).


Despite there being a large amount of evidence for the health effects that arise due to the ingestion of mycotoxins the effects of inhaled mycotoxins is a much more contentious issue, and large gaps remain in the knowledge base needed to conduct quantitative risk assessments for inhaled mycotoxins (Robbins et al., 2000). Although a great body of literature exists concerning the ingestion of mycotoxins by animals, there are few such studies of mycotoxin inhalation. In addition, results of these inhalation

toxicity studies are conflicting, with some reporting greater potency of mycotoxins via inhalation compared to other exposure routes, (Creasia et al., 1987, 1990) and with others reporting different results.(Mars et al., 1986; Pang et al., 1988). Until now, the only toxins detected in airborne dusts and bio aerosols have been trichothecenes of Stachybotrys chartarum, aflatoxins of Aspergillus flavus, and metabolites of A. fumigatus (Fischer and Dott, 2003).

Toxicity due to aflatoxins produced by Aspergillus flavus was first documented in 1960 and been the subject of extensive research because they are potent liver toxins and are carcinogenic by ingestion exposure (Robbins et al., 2000). Aflatoxins are found in a wide variety of crops used for human and animal consumption. One of the major diseases as a result of aflatoxin action is known as the turkey X disease. Diseases associated with aflatoxin by ingestion route include the acute syndrome of fatty liver, hepatic necrosis, and encephalopathy similar to Reyes syndrome. Chronic exposure to food contaminated with aflatoxins is associated with hepatocellular carcinoma (Fung and Hughson, 2003). Aspergillus parasiticus also produces aflatoxins. Aspergillus versicolor does not produce aflatoxin, but produces the aflatoxin precursor sterigmatocystin. In terms of animal studies on the effects of inhalation exposure to aflatoxins, studies of acute inhalation exposure (?120 min) to purified AFB1 have shown the formation of DNA adducts in the liver of rats (Zarba et al., 1992), and suppression of pulmonary and immune function in rats and mice (Jakab et al 1994). Mice exposed chronically (daily for one year) to aerosolized AFB1 had a 38 percent increase incidence of lymphatic leukaemia (Robbins et al., 2000).

One of the most high profile cases of believed mycotoxicosis in recent times was in Cleveland, Ohio where there was controversy concerning a possible link between stachybotrys mycotoxin exposure and acute pulmonary haemorrhage and death in infants (Fung et al., 1998). Because of this localised cluster of pulmonary haemorrhage incidents an epidemiologic study was initiated into the homes of the infants. It was found that the houses where these very young infants were living were water-damaged as a result of overflowing rain-swollen creeks in the area. There was evidence that water intrusion along with mould growth had occurred in the homes due to flooding, therefore it was proposed that the disease in these cases were the result of inhalation of Stachybotrys mycotoxin into the immature lungs of these small children (Etzel et al., 1998). These studies received considerable attention with widespread media coverage. However a Centre for Disease Prevention and Control (CDC) investigation later revealed serious shortcomings in the data suggesting a possible association between acute pulmonary haemorrhage and mould exposure was not proven (CDC, 2000).

Another example of work carried out to assess the health effects of inhaled mycotoxins were the studies conducted on the acute toxicity of T-2 toxin, T-2 toxin is a trichothecene. The trichothecenes are a group of structurally related mycotoxins with varying degrees of cytotoxic potency. They have a sesquiterpenoid ring structure, and can be classified according to the presence or absence of characteristic functional groups (WHO, 1990). Several common soil fungi, including Myrothecium rodium and Stachybotrys chartarum, are capable of producing macrocyclic trichothecenes. The T-2 toxin is also if significant importance in terms of its health effects when present in indoor environments due to its potential for use in chemical warfare (Robbins et al., 2000).

Although much concern has recently been generated in association with the detection of S. chartarum in indoor environments (Etzel, 2000), the assessment of hazard and exposure in these reports has consistently focused on toxigenic fungi (Dearborn et al, 2002), in contrast to the trichothecenes that certain species can produce. This distinction complicates their interpretation, because it is well established that the environmental detection of a toxigenic fungal species does not necessarily confirm the presence of mycotoxins (Tuomi et al., 2000). In one laboratory investigation of S. chartarum strains collected from indoor environments, the fungi producing the highest concentrations of macrocyclic trichothecenes were derived from the residences of healthy individuals (Jarvis et al., 1998).

In terms of animal studies of the health effects of inhaled T-2 toxin it was reported that for guinea pigs, the T-2 toxin LD50 for aerosol exposure (4 mg/kg) was about twice the LD50 for subcutaneous exposure (2mg/kg), however it was also reported that effects of acute inhalation and subcutaneous exposure to T2 toxin were quantitatively and qualitatively similar (Marrs et al., 1986).In contrast, it was later found for guinea pigs, that the T-2 toxin LD50 for aerosol exposure (0.4 mg/kg) was one-third of the LD50 for intraperitoneal injections (LD50 =1.2 mg/kg) (Creasia et al., 1990). These conflicting results may be due to the duration of inhalation exposure for a given total dose. The initial study exposed the guinea pigs for periods spanning 15 to 75 minutes, and noted a decrease in toxicity when dose was delivered over the longer time interval; however the later study exposed the guinea pigs for either 10 or 30 minutes. In the latter study, similarly exposed rats were even more sensitive to inhalation of T-2 toxin, which was 20 times more toxic than by the intraperitoneal route. In an earlier study by Creasia in (1987), the sensitivity of mice to inhaled T-2 toxin was similar to rats; and they too were more sensitive to exposures via inhalation (LD50 = 0.94 mg/kg) than exposures via the dermal or injection route with the LD50 > 10 mg/kg and LD50 = 4.5 mg/kg respectively (Creasia et al., 1987).

In another study using swine, it was projected that the LD50 would be higher by the inhalation route (>8 mg/kg) compared to intravenous exposure (1.2 mg/kg) (Pang et al., 1988). It was suggested that this apparent conflict with Creasias results may be due to differing susceptibilities of the animals, as well as differing time intervals used for the aerosol exposure (pigs were exposed for 45 to 61 minutes) (Pang et al., 1988).

Even though these animal studies are limited, they demonstrate some general trends. The results indicate that rats are more sensitive to inhaled T-2 toxin, followed by mice and then swine. It also appears that the toxicity resulting from inhalation exposure is dependent on the time interval of exposure for a given total dose, with greater toxicity for shorter exposures. This may be the result of more effective clearance and or metabolism of T-2 toxin by the lung at the lower airborne concentrations associated with longer exposure intervals. Exposures did not result in pulmonary oedema or gross histopathological changes in the lung; although the latter effects were seen in other organ systems, (Creasia et al., 1987; Creasia et al., 1990; Pang et al., 1988).It has been suggested that toxic effects are not seen in the lung because the toxin or toxin and vehicle is rapidly absorbed by the lung and quickly transported to other organs (Pang et al., 1988). Inhalation studies of mycotoxins in animals were designed to measure acute effects at high exposure levels, and these experimental exposures and associated effects do not represent exposures to mycotoxins at chronic, low exposure levels from moulds in indoor settings (Robbins et al., 2000).

These kinds of studies are useful in determining the range of response for different animals for a particular toxin at different doses and exposure time intervals. Although, they are only indirectly useful in examining the issue of exposure to mycotoxins from inhalation of mould spores. Unlike a pure mycotoxin aerosol, a mould spore is a complex assortment of chemicals that may act as synergists or inhibitors in producing toxic effects (Robbins et al., 2000).

In a later effort to better investigate the effect of mycotoxins from the inhalation of spores, mice were injected intranasally with S. chartarum spores (Nikulin et al., 2003). Mice were injected once with 106 spores in phosphate-buffered saline (PBS) of one of the two strains of S. chartarum that were used in this investigation. The first was s.72, a highly toxic strain, and the second was s.29, a strain that is only slightly toxic (the toxicity of each strain was determined by cytotoxicity tests). Control tests received PBS only. The s.72 strain contained satratoxins. All the mice receiving spores developed lung inflammation; however, there was a significant difference in the levels of inflammation between the two strains. The inflammation in the s.29-exposed mice were significantly milder than that produced by s.72, there was also necrotic damage that was only observed in the s.72-exposed mice (Nikulin et al., 2003).

The problem with these types of animal exposure models is that the significance and applicability of the results to actual inhalation exposures is limited because of the small number of animals used, the subjective grading of histological response, along with artificial and therefore non physiological exposure technique (injection), and method of spore quantification in the dose. The report by Nikulin et al (2003) further demonstrates that intranasal inoculation of large numbers of spores is unlikely to accurately reflect the exposure that humans are likely to encounter even very heavily fungal contaminated environments.

One notable and generally accepted exception that does occur through mould inhalation is pulmonary mycotoxicosis, this is often referred to as organic dust toxic syndrome (ODTS; Emanuel, 1975; Seifert et al., 2003). Organic Dust Toxic Syndrome (ODTS) is a flu-like illness following respiratory exposure to organic dusts. It was first reported in the mid-1970s (Emanuel, 1975) and has been accepted as a distinct clinical entity since the mid-1980s (May et al, 1986). Prior to its recognition as a clinical syndrome, particular instances were noted and characterized variously as pulmonary mycotoxicosis, silo unloaders syndrome, grain fever, toxin fever, humidifier fever, mill fever, toxic alveolitis, allergic alveolitis, and others (Terr et al, 2009). In 1994, the National Institute of Occupational Safety and Health (NIOSH) issued a report to increase the recognition of ODTS.

ODTS is an occupational disease of farmers in which mycotoxin concentrations are unknown although undoubtedly massive. This disease is a result of inhalation of mould spores (as well as bacteria and other microorganisms) within grain silos that may reach airborne concentrations of 105-10 fungal spores/m3. The exact mechanisms of toxicity are not known, but endotoxin, fungal spores, or mycotoxins are believed to play a role and the mechanism is non immunogenic (Von Essen et al., 1990). The amount and duration of exposure are important. Grain dust extracts have been shown to cause alveolar macrophages to produce IL-1, IL-6, and TNF-alpha, which are endogenous pyrogens (Von Essen et al., 1990). ODTS was associated with heavy exposure occurring on a single day, but there was no correlation between the individual spore types and development of the disease (Malmberg et al., 1993). Because of these conditions of exposure, pulmonary mycotoxicosis is likely to be complicated by exposure to bacterial endotoxins and possibly other toxins (Terr, 2009).

Peptidoglycan, endotoxin, and lipopolysaccharide (LPS) (both markers for microbial exposure and bioactive agents) were correlated with IL-6 production in. Peptidoglycan was correlated with increased peripheral white blood cell counts and body temperature and LPS was correlated with symptoms of ODTS (Seifert et al., 2003). In an investigation where three volunteers were exposed to wood chip mulch dust, their bronchoalveolar lavage (BAL) results showed increased IL-8 and IL-6. This suggests that cytokine networking in the lung may mediate ODTS (Wintermeyer et al., 1997). There may be a cascading effect, wherein activation of pulmonary macrophages triggers phagocytic responses with an infiltration of polymorphonuclear leukocytes in the lungs (Seifert et al., 2003). Complement may be activated and activated T-cells may release inflammatory mediators (Malmberg Malmberg et al., 1993; Seifert et al., 2003). An IgG-mediated reaction is unlikely, as there is an absence of specific precipitins (Seifert et al., 2003).

When comparing ODTS to calculations of airborne S. chartarum mycotoxin exposure for humans (not involved in ODTS), based on experimental data in mice, make it extremely unlikely that toxic concentrations would occur within buildings (ACOEM, 2002), even those severely contaminated by mould from excessive water intrusion or dampness.

Infection by airborne fungi

Infection primarily is the entry and multiplication of a biological agent in this case a fungal organism, in a hosts body. Systemic fungal infections such as histoplasmosis, coccidioidomycosis, and cryptococcosis can occur when people are exposed to contaminated bird droppings or construction dusts. These environmental fungi Coccidiodes (soil), Cryptococcus (bird droppings) and Histoplasma (bat droppings) may infect normal people. However these are outdoor fungi and are not usually reported as a biological health hazard in indoor environments, despite this, theoretically these fungi may be brought indoors (Fung and Hughson, 2003). However opportunistic mycoses are primarily restricted to severely immunocompromised subjects and therefore they are associated with a much higher risk in hospital environments. Deep-tissue invasion of fungi can occur to severely immunocompromised individuals with lympho proliferative disorders such as leukaemia or cancer patients receiving chemotherapy, and those who are receiving immunosuppressive treatment for bone marrow or organ transplantation (Walsh Walsh and Dixon 1989; Singh, 2001; Fung and Hughson, 2003).

In terms of invasive fungal disease in immunocompromised patients one of the most commonly encountered fungi are Aspergillus spp. Due to their ubiquitous nature in normal outdoor and indoor environments. And when examining autopsy surveys it has been documented that there has been a dramatic increases in the incidence rates of invasive aspergillosis during the recent years starting from less than 0.4% of all patients autopsied in the seventies up to 4% in the mid-nineties (Yamazaki et al., 1997) (Groll et al., 1996). Also it has been shown that in a recent population-based laboratory active surveillance that the one-year cumulative incidence of invasive aspergillosis is estimated at 12.4 per million persons (Rees et al., 1998).

The primary route of acquiring Aspergillus infection is most likely by the inhalation of fungal spores. Spores of the most commonly involved pathogenic Aspergillus spp. such as Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus, are relatively small, with sizes ranging from 25 microns (VandenBergh et al., 1999). When inhaled, spores can become deposited in both the upper and lower respiratory tract (Morrow 1980). Usually in most individuals deposited airborne spores will be cleared without the onset of any negative health effects. However, immunocompromised patients are extremely susceptible to local invasion of respiratory tissues by deposited spores, and this results in invasive aspergillosis (VandenBergh et al., 1999).

Specific factors influencing areas of high risk

Areas of high risk are generally those that have factors leading to an increased level of biological contaminants in the air. One of the major factors that lead to an increase in indoor biological air contamination is the presence of water within the building, especially water damage. The building materials also play a significant role in the prevalence on airborne fungal contamination, for example a study by Meklin et al., (2003) comparing the visible mould and water damage as well as airborne fungal contamination between wooden and concrete or brick school buildings. From this investigation it can be seen that the frame material of the building was a determinant of airborne micro flora. The mean concentrations of viable airborne fungi were significantly higher in wooden schools, resulting mainly from higher concentrations of the most common fungi, including, Penicillium, yeasts, Cladosporium, and nonsporing isolates, also more frequently in the wooden schools was detection of Wallemia, Olpitrichum, Oidiodendron, Hyalodendron, Paecilomyces, and the Sphaeropsidales group. Actinobacteria concentrations were also higher in wooden schools compared with concrete schools.

Another area of high risk when considering contamination of indoor air is in a hospital environment The control of microbial air contamination in hospital wards is of great importance particularly for hospital infections where an airborne infection route is hypothesised, such as aspergillosis. Invasive aspergillosis represents one of the most serious complications in immunocompromised patients (Pini et al., 2004). The risk of a hospital environment for the acquisition of infection from airborne sources can be seen in Italy where it has been estimated that, in approximately 8 million patients hospitalised annually, there are 369,000 hospital infections found (Pini et al., 2004). In hospital patients the risks of infection linked to environmental aero contamination are mostly associated to the fungi of the Aspergillus genus (A. fumigatus, A. terreus, A. flavus), responsible for disseminated or localised infections which have often

been described in hospitalised immunodepressed patients (Walsh and Dixon, 1989; Vonberg and Gastmeier, 2006). These fungi are capable of reproducing on different kinds of substrates, such as decaying vegetation and ornamental plants. They have also been found and isolated from air conditioning, humidifying and ventilation systems (Arnow et al., 1999; Parat Arnow et al., 1999).

Fungal contamination inside hospitals is the result of a combination of various factors that are difficult to investigate, however it has been established that hospital infections caused by Aspergillus spp. occur with greater frequency when construction work in hospital wards are taking place or have just been completed (Oren et al., 2001). This has been associated with the increase of dust in the air which facilitates the spreading of any fungal particles already present.

Invasive aspergillosis represents a major problem in particular for those patients with a serious and lengthy neutropenia (patients who with leukaemia or have undergone blood-marrow transplants) (Bodey et al., 1992). The diagnosis of this type of infection is difficult and often late (Klont et al., 2001), for which reason, therapy in many cases is ineffective and mortality exceeds 50% (Lin et al., 2001). To prevent nosocomial aspergillus infections, high-risk patients are usually placed in protective isolation rooms in which there is always a positive air pressure maintained compared with surrounding areas (Humphreys, 2004). These special rooms are provided with high-efficiency particulate air (HEPA) filters and an air flow of at least 12 air changes/h as HEPA filtration significantly reduces the concentration of fungal spores and the incidence of invasive aspergillosis (Withington et al., 1998; Cornet ,1999). In addition, horizontal laminar air flow (LAF) is provided in some facilities which drive contaminants out through the ducts (Vonberg and Gastmeier, 2006). However, additional protection due to LAF remains a matter of debate and the use of LAF is not explicitly recommended by the Centres for Disease Control and Prevention (CDC), the Infectious Disease Society of America (IDSA) or the American Society of Blood and Marrow Transplantation (ASBMT) for the care of haematopoietic stem cell transplant recipients (Vonberg and Gastmeier, 2006).