Exposure to indoor fungi and their biochemical products may occur by means of one or more routes or 'pathways': 1) inhalation (breathing of inhaled spores, spore fragments, or volatile compounds), 2) absorption or dermal contact (contact with skin), and 3) ingestion (consuming contaminated materials).  Inhalation and dermal contact represent the most probable exposure pathways for occupants under typical indoor conditions.  

The presence of fungi on indoor building materials does not present unequivocal proof of exposure.  Cells, spores, cell fragments, or metabolites must first come in contact with the occupant.   This is often achieved by direct contact with contaminated materials or by indirect contact after contaminants become aerosolized and disperse to areas not directly affected by fungal growth or water damage.  Depending on the location and extent of contamination, air currents within buildings and homes as well as normal occupant activities are sufficient to disperse fungal contaminants.  Remediation activities may cause even greater releases of aerosolized microbes (Rautiala et al, 1996).  Microbial contamination within concealed building cavities also poses concerns for occupant exposure as spore dispersal may occur via through-wall openings and structural joints.  Exposure assessments must also account for the fact that nonviable (i.e. dead) spores retain their allergenic, irritant, and toxigenic properties.   The viability of fungal contaminants is therefore irrelevant when considering risks other than infection.  Cell or spore fragments, which are not measured by routine sampling, also retain their physical properties.  Cell fragments may actually present even greater risks because their smaller size enables deeper penetration into airway passages (Gorny et al., 2002).  Furthermore, many common contaminants produce metabolites called Volatile Organic Compounds (VOCs) that readily migrate through building materials such as wood sheathing, concrete, drywall, and even plastic vapor barriers.

Health effects caused by fungal contaminants are difficult to predict and reactions depend on several important variables such as duration and frequency of exposure, concurrent exposures to other sources (e.g. outdoor fungi), the type of agents involved, the physiological condition of the agent, and the sensitivity of the exposed individual.  Still, it is well established that fungi cause or exacerbate numerous ailments (Ajello and Hay, 1998; AAP, 1998; Apostolakos et al., 2001; Burge and Ammann, 1999; Bush and Prochnau, 2004; Croft et al., 2002; Gent et al., 2002;  Hardin et al., 2003; Henderson et al., 1988; Horner, et. al., 1995; Institute of Medicine, 2004; Kuhn and Ghannoum, 2003; Lee et al., 2000; Lin and Williams, 2003; Patterson et al.,  1981; Rylander and Lin, 2000; Saini et al., 1998; Woodard et al., 1988; Yang and Johanning, 1996).   Examples of suspected mold-related effects include cough, congestion, wheezing, chest tightness, runny nose, headaches, flu-like symptoms, muscle and joint pain, fatigue, dizziness, nosebleeds, eye irritations, infections, confusion, memory loss, and anxiety.  Furthermore, exposures to fungal antigens and irritants such as proteins, fungal glucans, mycotoxins, and other secondary metabolites may have complex results with unknown etiological mechanisms.

As recent as 2004, The Institute of Medicine completed a comprehensive review of the medical literature and found that the current evidence links mold to a variety of adverse health effects.   Exposures were associated with asthma, coughing, wheezing, upper respiratory tract symptoms, and hypersensitivity pneumonitis.  At the time of this study, insufficient information existed to establish a clear association with a wider array of symptoms such as fatigue and neuro-psychiatric disorders.   More recent peer-reviewed research demonstrates that airborne exposures to fungi/mycotoxins may alter human behavior, neurophysiology, immunology, and pulmonary function (Curtis et al., 2004;  Dennis, 2003, Gray et al., 2003;  Kilburn, 2003; Rea et al., 2003; Vojdani et al., 2003).
 

Allergy

Indoor fungal contaminants may cause short and long-term hypersensitive reactions (allergies).  Hypersensitive reactions are exaggerated immune responses resulting in tissue inflammation or damage.  Such responses are categorized based on the timing of the reaction as well as the nature of the immune components involved.  The most common allergenic responses caused by fungi include Type I, Type III, and Type IV hypersensitivities (Burge and Otten, 1999; Horner et al., 1995; Yang and Johanning, 1996). Type I hypersensitivities involve an immediate but localized response to allergens such as fungi, pollen, dust mites, or animal dander.  By virtue of common components of spore walls, most fungi are capable of causing Type I reactions.  Type I responses are mediated by a particular class of circulating antibodies or “immunoglobulins” referred to as IgE, which can be detected directly by antigen-specific analyses of blood serum or indirectly by allergy skin tests.  Common symptoms of a Type I response include itchy or watery eyes, runny nose, sinusitis, coughing or sneezing, congestion, chest tightness, and shortness of breath.

Type III hypersensitivities involve delayed responses (usually within hours or days) caused by the formation of insoluble antigen-antibody complexes.  These complexes migrate within the blood stream and may eventually cause acute inflammation, constriction of blood vessels, and tissue necrosis.  Such reactions may persist for weeks or even months following the last known exposures.  Examples of this type of disorder include Hypersensitivity Pneumonitis and extrinsic allergic alveolitis which are caused by wide variety of fungi, other microorganisms, and non-biological agents.  Type III reactions are mediated primarily by antibodies referred to as IgG and IgM, which are best assessed by antigen-specific analyses of blood serum.  Symptoms of Type III hypersensitivities may include fatigue, muscle and joint pain, respiratory disorders, chest pressure, and general flu-like symptoms.

Type IV hypersensitivity, as with the Type III, represents a ‘delayed’ reaction.  But unlike Type I and Type III reactions, Type IV hypersensitivities are not mediated by antibodies.  Instead, Type IV reactions are mediated by T-Cells, a type of lymphocyte produced in bone marrow and modified within the thymus.  Delayed hypersensitive reactions are wholly or partly responsible for extrinsic allergic alveolitis and contact dermatitis - a common skin disorder.

Irritation

Irritants are biological, physical, or chemical substances that cause cellular changes in epithelial, connective, nervous, or muscle tissue.  Although the terms “irritant” and “allergen” are often used synonymously, the term “irritant” is typically used to denote symptoms that cannot be diagnosed or explained by other etiological mechanisms, including immune responses.  Because conditions caused by allergens and irritants are manifested as similar inflammatory responses, careful evaluation is necessary for differentiation. For example, conditions such as bronchitis, rhinitis, sinusitis, and conjunctivitis (inflammation of the eye) are the result of allergic and irritant (non-allergic) responses.  Common ‘allergy’ symptoms such as airway constriction, headache, fatigue, nausea, and memory loss, and inability to concentrate are also caused by non-allergens (i.e. irritants or toxins).  In many instances multiple etiological mechanisms and their respective symptoms may coexist and the cause might not be distinguished by routine or even specialized medical evaluations.  Diagnostics for irritants such as VOCs, mycotoxins, endotoxins, or other cell wall constituents may be altogether lacking; and therefore it may be extremely difficult to establish definitive causation.   

Most fungal contaminants produce spores, cell wall constituents, VOCs, and other metabolites that cause irritations in a wide variety of tissue types.  Of particular concern are irritations caused by Beta-D-Glucans and VOCs (Volatile Organic Compounds).  Glucans represent structural components in cell walls of most fungi as well as some bacteria and plants.  Glucan exposures are expected wherever fungi occur in high abundance.  Symptoms such as chest tightness, cough, shortness of breath, and wheezing are suggestive of glucan inhalation in susceptible individuals or for otherwise healthy individuals exposed to high levels of airborne fungi (Burge and Ammann, 1999; Rylander and Lin, 2000).  Volatile organic compounds are chemical irritants responsible for the moldy or musty odors often associated with microbial contamination.  Other common odors are described as being chemical, sweet, or pungent.  It is important to note that not all VOCs are detectable by human sensory receptors.  In other words, the absence of odors does not rule out the possibility of irritant effects.  Examples of VOCs produced by fungal contaminants include hexanol, benzene, toluene, acetone, 2-butanone, cyclohexane, and ethanol.  Although the etiological mechanisms remain poorly defined, some of the symptoms of VOC-exposure include headache, nausea, rhinitis (runny nose), acute or chronic respiratory effects, attention deficit, and inability to concentrate (Ammann, 1999). 

Toxicity

Many species of fungi produce cell wall substances (e.g. proteins and glucans) and secondary metabolites (e.g. mycotoxins and volatile organic compounds) that are toxic to humans and other animals (Burge and Ammann, 1999).  Because glucans and mycotoxins have low volatility they are not readily removed from the spore.  So it is presumed that wherever spores are found, toxic cell wall components are also present.  As previously discussed, fungal cells/spores retain their toxigenic properties regardless of whether the cell is actually alive or dead.

Mycotoxins are toxic metabolites produced by certain species of fungi.  Although a given fungal species may produce several mycotoxins, a particular mycotoxin is often produced by more than one genus or species.  Toxin production is also highly variable with regards to environmental conditions and the metabolized substrate.  As a precautionary measure, it is assumed that if toxigenic species are present, the associated mycotoxins may also be present.  Still, irritant or toxic effects are dependent on a number of variables including the toxin type and concentration, the exposure pathway, and the susceptibility of exposed individuals. Epidemiological investigations involving airborne exposures suggest that mycotoxins cause a variety of human diseases.  The significance of these findings has been previously assessed by several peer-reviewed publications (American Academy of Pediatrics, 1998; Burge and Ammann, 1999; Health Canada, 1995; Hendry and Cole, 1993; Yang and Johanning, 1996).  Complaints associated with mycotoxins include depression, headaches, fatigue, muscle and joint pains, nausea, and upper or lower respiratory disorders. Other symptoms may include chills, fever, tremors, sensitized skin, numbness, vasoconstriction, nosebleeds, blood in feces or urine, immune dysfunction, and altered conditions involving the central and peripheral nervous systems. 

Despite the growing evidence supporting a causal relationship between airborne mycotoxins and health effects (Croft et al., 2002), mycotoxicosis due to inhalation of indoor spores remains highly controversial (Robbins et al., 2000; Hardin et al., 2003).  The amount of toxins contained in aerosolized spores, even at high levels, may be insufficient to cause classical mycotoxin poisoning such as that caused by mycotoxin-contaminated food.  Nonetheless, many mycotoxin-related effects may actually involve mechanisms not explained by conventional dose-response models.  In other words, the mycotoxins could act as irritants or allergens, or the toxic response may not be detectable by conventional medical evaluation.  The synergistic effects of mycotoxins, VOCs, and fungal glucans also remain unknown and it is conceivable that such complex mixtures could account for effects that are otherwise unsubstantiated by quantified mycotoxin concentrations in sampled spores.  

Exposures to complex and nonspecific mixtures of compounds such as fungal toxins, bacterial endotoxins, fungal proteins, and beta(1-3)-D-Glucans may result in non-allergenic, noninfectious lung reactions termed Organic Dust Toxic Syndrome (ODTS).  The clinical features of ODTS resemble a flu-like illness and include breathing difficulty, cough, headaches, fever & chills, fatigue, acute inflammatory lung reaction, and negative chest X-ray (Burge and Ammann, 1999; Yang and Johanning, 1996).  The symptoms of ODTS (also called toxic pneumonitis) are also very similar to a hypersensitive reaction called hypersensitivity pneumonitis or extrinsic allergic alveolitis; however, ODTS differs by being nonallergenic, thus high antibody precipitins are not formed.  

INFECTION

Fungal infections in healthy individuals are relatively rare.  Nonetheless, common fungal contaminants still represent potentially infectious agents that are capable of causing localized and systemic infections in susceptible individuals (Ajello and Hay, 1998; Henderson et al., 1988; Saini et al., 1998).  Conditions such as antibiotic treatment, steroid treatment, chemotherapy, and immune disorders are examples of predisposing or susceptible or pre-disposed states.  Children, pregnant women, and elderly individuals also show greater susceptibility. 

LITERATURE CITED

Click Here to View Literature