Heath Effects of Toxic Mold
Exposure to fungi and mycotoxins can, depending on dose and duration of exposure cause ill health or aggravate conditions including:
Opportunistic Mycosis (non-contagious; skin)
Organic Dust Toxic Syndrome
Skin and Mucous Membranes
Death in Human and Animals
The most common response to mold exposure may be allergy. People who are atopic, that is, who are genetically capable of producing an allergic response, may develop symptoms of allergy when their respiratory system or skin is exposed to mold or mold products to which they have become sensitized. Sensitization can occur in atopic individuals with sufficient exposure.
Allergic Reactions can range from mild, transitory responses, to severe, chronic illnesses. The Institute of Medicine (1993) estimates that one in five Americans suffers from allergic rhinitis, the single most common chronic disease experienced by humans. Additionally, about 14 % of the population suffers from allergy-related sinusitis, while 10 to 12% of Americans have allergically-related asthma. About 9% experience allergic dermatitis. A very much smaller number, less than one percent, suffer serious chronic allergic diseases such as allergic bronchopulmonary aspergillosis (ABPA) and hypersensitivity pneumonitis (Institute of Medicine, 1993). Allergic fungal sinusitis is a not uncommon illness among atopic individuals residing or working in moldy environments. There is some question whether this illness is solely allergic or has an infectious component. Molds are just one of several sources of indoor allergens, including house dust mites, cockroaches, effluvia from domestic pets (birds, rodents, dogs, cats) and microorganisms (including molds).
While there are thousands of different molds that can contaminate indoor air, purified allergens have been recovered from only a few of them. This means that atopic individuals may be exposed to molds found indoors and develop sensitization, yet not be identified as having mold allergy. Allergy tests performed by physicians involve challenge of an individual's immune system by specific mold allergens. Since the reaction is highly specific, it is possible that even closely related mold species may cause allergy, yet that allergy may not be detected through challenge with the few purified mold allergens available for allergy tests. Thus, a positive mold allergy test indicates sensitization to an antigen contained in the test allergen (and perhaps to other fungal allergens) while a negative test does not rule out mold allergy for atopic individuals.
Type 1 Allergies
Immediate type - hypersensitivity. Fungi may cause allergic rhinitis similar to that caused by pollen grains, and, after asthmatics become allergically sensitized to one or more of them, they may trigger asthma attacks. Most asthmatics have multiple allergies.
Type 3 Allergies
Delayed type hypersensitivity. In certain susceptible individuals, after prolonged, heavy exposure, fungi may cause hypersensitivity pneumonitis (allergic alveolitis), characterized by wheeze, shortness of breath, cough, chest tightness, and in some prolonged cases, pulmonary fibrosis. There has been a custom of giving each new subtype of hypersensitivity pneumonitis (HP) an evocative medical nickname, such as farmer's lung, maple bark stripper's disease, and so on. "Humidifier fever" is the most common such name associated with indoor mold proliferation, since HP is often associated with contaminated humidifiers. HP has also, however, been reported from indoor mold proliferations on structural or furnishing elements, such as walls or shower curtains. A HP patient should have strong serum precipitins specific to the fungus (or bacterium or protozoan) which is causing the reaction. Bronchioalveolar lavage or biopsy will usually show elevated numbers of eosinophil cells, showing eosinophilic immune activation.
Persons who have been asthmatic for many years may progress to have their bronchial passages colonized by a fungus, usually Aspergillus fumigatus, but sometimes another organism such as Bipolaris hawaiiensis, Wangiella dermatitidis, or Pseudallescheria boydii. Constant allergic response helps to maintain the fungal colonization, and first-line therapy is often with steroids: bringing down the level of inflammation may result in elimination of the colonizing organism. Some studies have made tentative links between exacerbations of ABPA and moldy houses. Cystic fibrosis patients also may get allergic bronchopulmonary mycosis.
Allergic Mycotic Sinusitis
A colonizing infection of mucus adhering to the sinus walls. Very similar to ABPA otherwise, except that patients need not necessarily have had asthma or cystic fibrosis. To date no discrete connection with indoor mold proliferation has been shown in any individual cases, but that may be from lack of investigation.
From molds that grow in indoor environments is not a common occurrence, except in certain susceptible populations, such as those with immune compromise from disease or drug treatment. A number of Aspergillus species that can grow indoors are known to be pathogens. Aspergillus fumigatus (A. fumigatus) is a weak pathogen that is thought to cause infections (called aspergilloses) only in susceptible individuals. It is known to be a source of nosocomial infections, especially among immune-compromised patients. Such infections can affect the skin, the eyes, the lung, or other organs and systems. A. fumigatus is also fairly commonly implicated in ABPA and allergic fungal sinusitis. Aspergillus flavus has also been found as a source of nosocomial infections (Gravesen et al., 1994). There are other fungi that cause systemic infections, such as Coccidioides, Histoplasma, and Blastomyces. These fungi grow in soil or may be carried by bats and birds, but do not generally grow in indoor environments. Their occurrence is linked to exposure to wind-borne or animal borne contamination.
Adverse Reactions to Odor
Odors produced by molds may also adversely affect some individuals. Ability to perceive odors and respond to them is highly variable among people. Some individuals can detect extremely low concentrations of volatile compounds, while others require high levels for perception. An analogy to music may give perspective to odor response. What is beautiful music to one individual is unbearable noise to another. Some people derive enjoyment from odors of all kinds. Others may respond with headache, nasal stuffiness, nausea or even vomiting to certain odors including various perfumes, cigarette smoke, diesel exhaust or moldy odors. It is not know whether such responses are learned, or are time-dependent sensitization of portions of the brain, perhaps mediated through the olfactory sense, or whether they serve a protective function. Asthmatics may respond to odors with symptoms.
Mucous Membrane and Trigeminal Nerve Irritation
A third group of possible health effects from fungal exposure derives from the volatile compounds (VOC) produced through fungal primary or secondary metabolism, and released into indoor air. Some of these volatile compounds are produced continually as the fungus consumes its energy source during primary metabolic processes. (Primary metabolic processes are those necessary to sustain an individual organism's life, including energy extraction from foods, and the syntheses of structural and functional molecules such as proteins, nucleic acids and lipids). Depending on available oxygen, fungi may engage in aerobic or anaerobic metabolism. They may produce alcohols or aldehydes and acidic molecules. Such compounds in low but sufficient aggregate concentration can irritate the mucous membranes of the eyes and respiratory system. Just as occurs with human food consumption, the nature of the food source on which a fungus grows may result in particularly pungent or unpleasant primary metabolic products. Certain fungi can release highly toxic gases from the substrate on which they grow. For instance, one fungus growing on wallpaper released the highly toxic gas arsine from arsenic containing pigments.
Fungi can also produce secondary metabolites as needed. These are not produced at all times since they require extra energy from the organism. Such secondary metabolites are the compounds that are frequently identified with typically "moldy" or "musty" smells associated with the presence of growing mold. However, compounds such as pinene and limonene that are used as solvents and cleaning agents can also have a fungal source. Depending on concentration, these compounds are considered to have a pleasant or "clean" odor by some people. Fungal volatile secondary metabolites also impart flavors and odors to food. Some of these, as in certain cheeses, are deemed desirable, while others may be associated with food spoilage. There is little information about the advantage that the production of volatile secondary metabolites imparts to the fungal organism. The production of some compounds is closely related to sporulation of the organism. "Off" tastes may be of selective advantage to the survival of the fungus, if not to the consumer.
In addition to mucous membrane irritation, fungal volatile compounds may impact the "common chemical sense" which senses pungency and responds to it. This sense is primarily associated with the trigeminal nerve (and to a lesser extent the vagus nerve). This mixed (sensory and motor) nerve responds to pungency, not odor, by initiating avoidance reactions, including breath holding, discomfort, or paresthesias, or odd sensations, such as itching, burning, and skin crawling. Changes in sensation, swelling of mucous membranes, constriction of respiratory smooth muscle, or dilation of surface blood vessels may be part of fight or flight reactions in response to trigeminal nerve stimulation. Decreased attention, disorientation, diminished reflex time, dizziness and other effects can also result from such exposures (Otto et al., 1989). It is difficult to determine whether the level of volatile compounds produced by fungi influence the total concentration of common VOCs found indoors to any great extent. A mold-contaminated building may have a significant contribution derived from its fungal contaminants that is added to those VOCs emitted by building materials, paints, plastics and cleaners. Miller and co-workers (1988) measured a total VOC concentration approaching the levels at which Otto et al., (1989) found trigeminal nerve effects. At higher exposure levels, VOCs from any source are mucous membrane irritants, and can have an effect on the central nervous system, producing such symptoms as headache, attention deficit, inability to concentrate or dizziness.
Vascular System - increased vascular fragility, hemorrhage into body tissues, or from lung, e.g., aflatoxin, satratoxin, roridins
Digestive System - diarrhea, vomiting, intestinal hemorrhage, liver effects, i.e., necrosis, fibrosis: aflatoxin; caustic effects on mucous membranes: T-2 toxin; anorexia: vomitoxin.
Respiratory System - respiratory distress, bleeding from lungs e.g., trichothecenes Nervous system, tremors, incoordination, depression, headache, e.g., tremorgens, trichothecenes.
Cutaneous System - rash, burning sensation sloughing of skin, photosensitization, e.g., trichothecenes Urinary system, nephrotoxicity, e.g. ochratoxin, citrinin.
Reproductive System - infertility, changes in reproductive cycles, e.g. T-2 toxin, zearalenone.
Immune System - changes or suppression: many mycotoxins. It should be noted that not all mold genera have been tested for toxins, nor have all species within a genus necessarily been tested. Conditions for toxin production varies with cell and diurnal and seasonal cycles and substrate on which the mold grows, and those conditions created for laboratory culture may differ from those the mold encounters in its environment. Toxicity can arise from exposure to mycotoxins via inhalation of mycotoxin-containing mold spores or through skin contact with the toxigenic molds. A number of toxigenic molds have been found during indoor air quality investigations in different parts of the world. Among the genera most frequently found in numbers exceeding levels that they reach outdoors are Aspergillus, Penicillium, Stachybotrys, and Cladosporium. Penicillium, Aspergillus and Stachybotrys toxicity, especially as it relates to indoor exposure.
Glucan Effects - Beta-1, 3-glucan is a major structural component of almost all fungal cell walls. It is a polymer of glucose similar to cellulose, but with less tendency to be found in strands. It bears considerable structural similarity to very toxic molecules known as endotoxins secreted by some bacteria, particularly some gram-negative organisms. This similarity caused an endotoxin expert, Dr. Ragnar Rylander, to investigate it as a possible candidate for the chemically irritating component found in mold conidia. It was found to activate PAMs, possibly making the lungs hyperreactive to a wide variety of foreign materials. Also, in double-blind inhalation exposure trials conducted with human volunteers, exposure correlated significantly with some non-specific respiratory symptoms. The most strongly correlating symptom, however, was headache. The contribution of glucans to indoor mold irritation is still under investigation; glucan effects may add to or synergize mycotoxin effects, or may be mistaken for mycotoxin effects in fungi where the actual amount of mycotoxin present in conidia is not sufficient to cause symptoms.
Volatile Chemical Effects
Volatile Chemical Effects - Most molds, especially those with dry conidia, produce volatile odor constituents. In a few cases, these are fruity or flowery and may be adapted to attract arthropod dispersers (e.g. insects carrying the mold conidia to new growth sites). Usually they are musty or earthy and are probably adapted to deter grazing and feeding invertebrates and vertebrates, or at least to give a distinct "not food" odor to mold colonies and their underlying nutritional substrates. A few such volatiles have been found to be directly irritating to vertebrates. Apart from experiencing such direct physiological irritation, humans and other vertebrates may be adapted to avoid such odors, and there may be a legitimate "psychological" objection to their presence in rooms. Mold growth in buildings may be accompanied by the growth of Streptomyces species, which usually have very strong earthy volatile odours. In addition, in very wet materials, copious bacteria may grow and may emit typical rotten or sour smelling odour molecules.
Invasive Pathogenesis - Of the regularly occurring indoor mold proliferation species, only a few have significant potential as opportunistic pathogens, and even these usually require a relatively strongly immuno compromised patient before they can be regarded as dangerous. Warm, moist environments, such as dirty heating ducts affected by condensation, or vanes and other apparati near heating system humidifiers, may grow Aspergillus fumigatus, the best known opportunistic mold fungus. This species also tends to occur in potted plant soils, particularly where these have not been exchanged for fresh soils (e.g., by re-potting) for several years. Usually, a patient needs to have a relatively high degree of neutropenia (deficit in neutrophil type white blood cells, an essential component of the immune system) before he or she is seriously threatened with invasive disease by this organism. Most such patients are persons taking leukemia chemotherapy or drugs designed to prevent rejection of transplanted organs. Occasionally other predisposing factors are found, such as heavy, prolonged corticosteroid use. AIDS patients are at little risk for such diseases unless they develop lymphomas or are taking potentially neutropenia-inducing drugs such as ganciclovir.
In recent years, because of the emergence of antibiotic-resistant bacteria in hospitals, some hospitals have begun to send severely neutropenic patients home. These patients are at high risk of infection by indoor infestations of A. fumigatus, A. niger, A. nidulans, A. flavus, A. terreus, Pseudallescheria boydii, Fusarium solani, F. oxysporum, F. moniliforme, F. proliferatum, and some other species. People who do not have these specific immuno-compromising conditions, however, are not at significant risk of invasive disease from any of these fungi (with the possible exception of P. boydii punctured into the dermis or the eye).
Community Effects - Fungally colonized materials often support a large population of arthropods, usually fungivorous (fungus-eating) mites, but also other arthropods such as booklice, millipedes and beetles (a recent sticky tape sample sent to this author from the wall of a moldy house contained a lawn of Cladosporium which was being grazed on by the drugstore beetle, Stegobium panacaea. The insect's faecal deposits consisted entirely of mold conidia). The growth of the house dust mite, Dermatophagoides pteronyssimus, in carpets,mattresses and dust accumulations may be stimulated by growth of xerotolerant (drought-tolerant) aspergilli such as A. glaucus on human skin scale litter and other dry household organic particulates. Arthropod body parts and faeces may be highly allergenic, and house dust mite in particular is well known to be highly irritating to most asthmatic children.
Medical Evaluation - Individuals with persistent health problems that appear to be related to fungi or other bioaerosol exposure should see their physicians for a referral to practitioners who are trained in occupational/environmental medicine or related specialties and are knowledgeable about these types of exposures. Infants (less than 12 months old) who are experiencing non-traumatic nosebleeds or are residing in dwellings with damp or moldy conditions and are experiencing breathing difficulties should receive a medical evaluation to screen for alveolar hemorrhage. Following this evaluation, infants who are suspected of having alveolar hemorrhaging should be referred to a pediatric pulmonologist. Infants diagnosed with pulmonary hemosiderosis and/or pulmonary hemorrhaging should not be returned to dwellings until remediation and air testing are completed. Clinical tests that can determine the source, place, or time of exposure to fungi or their products are not currently available. Antibodies developed by exposed persons to fungal agents can only document that exposure has occurred. Since exposure to fungi routinely occurs in both outdoor and indoor environments, this information is of limited value.