Mold Toxicity: Pathways, Diseases, & Interventions

Man with paintbrush painting wooden house exterior, ensuring dry environment to reduce the risk of mold growth.
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Mold, fungi, and bacteria that thrive in damp environments with inadequate ventilation emit spores, allergens, mycotoxins, endotoxins, ?-glucans, and microbial volatile organic compounds into the air.1 These submicron fungal fragments (fine fungal particles of less than 1 µm) may contribute to adverse health effects like asthma due to their small size and biological composition.2 Fungal fragments can stay airborne longer than fungal spores, which are larger, and can penetrate deeply into lungs and be deposited due to their small aerodynamic diameter.2

Evidence suggests these emissions may act as inflammatory mediators and may damage airways, leading to respiratory disease.3 The causative agents of adverse health effects involving mold have not been identified conclusively, but the World Health Organization considers an excess level of any of these agents in the indoor environment a potential health hazard.1 Extreme dampness, mold, and fungal fragments also contribute to indoor air pollution, which is considered a major cause of morbidity and mortality worldwide.1

Mold, which is a specific type of microscopic fungi, can thrive on any organic matter, including clothing, leather, paper, and the ceilings, walls, and floors of homes with moisture management problems.4 Mold is unable to digest inorganic materials (such as concrete, glass, and metal), but it can digest and grow on the dirt, dust, and organic residue that accumulates on these materials.4 In a 2009 report, the WHO estimated that 10% to 50% of indoor environments in Europe, North America, Australia, India, and Japan have clinically significant mold problems, with even higher percentages in river valleys and coastal areas.1,5 The primary indicators of dampness and microbial growth are:

  • Condensation on surfaces or in structures such as windows
  • Visible mold, especially black mold
  • Perceived moldy odor
  • Poorly maintained air conditioning systems
  • A history of water damage (exterior leaks, wet basement, leaking plumbing)1

Asthma & Allergic Respiratory Diseases

Dampness and mold hypersensitivity syndrome (DMHS) typically presents with mild to moderate signs of irritation of the respiratory tract and/or the eyes.6 As the condition progresses, it may become chronic.6,7 The health effects of DMHS may include allergic respiratory diseases, asthma, allergic rhinitis, exogenous allergic alveolitis, and respiratory tract infections/bronchitis.8

DMHS is characterized by a dysregulated immune system that favors hypersensitivity and which may manifest as an increased susceptibility to infection.9 Fungal components that serve as allergens may also trigger an IgE response that contributes to asthma development and asthma severity.7,10 Some research suggests that fungi can bind to antibodies, allowing them to be recognized by cells of the innate immune system, including macrophages, dendritic cells, and mast cells, which are then stimulated via toll-like receptor signaling.11,12 Fungi may activate the immune system directly or through mycotoxins and may also cause diseases mediated by mast cells and aggravate allergic inflammation.11,12 Specifically, mast cells activated by fungi may provoke an increase of prostaglandin D2 levels and lead to hypersensitivity diseases, which present signs such as irritation of the respiratory tract and eyes, recurrent sinusitis, bronchitis, and cough.12 Mold may also liberate mycotoxins that could exist on volatile spores and stimulate mast cells to secrete pro-inflammatory cytokines/chemokines.11 However, the precise mechanism of action of this activation is not well understood.

The majority of peer-reviewed published research on mold is in relation to respiratory conditions, and that research suggests that mold and damp building exposure is a major factor in the asthma epidemic.5 It has been estimated that 21% of current asthma cases in the US are attributable to dampness and mold (4.6 million of 21.8 million).13,14 A more recent meta-analysis of longitudinal studies concluded for the first time in children that there was sufficient evidence of a causal relationship between exposure to indoor molds and the development and exacerbation of asthma.15 In adults, the authors concluded that there was sufficient evidence of an association for asthma in relation to work in a moldy and damp building.15

It is important to note that while many studies have shown consistent associations between evident indoor dampness or mold and respiratory or allergic health effects, causal links remain somewhat unclear.10,16 This may be due, in part, to the historically limited research on the interactions between genes and mold exposure on childhood asthma.17 However, a 2021 case-control study in Shanghai, with 645 asthmatic children and 910 non-asthmatic children aged 3-12 years old, found that both visible mold exposure and rs7216389 polymorphism increased the risk of childhood asthma. Moreover, the effect of visible mold exposure on asthma became more prominent in children carrying the rs7216389 T allele.17 The relative excess risk contributed by the additive interaction between the rs7216389 risk genotypes and visible mold exposure was 1.49 (95% CI 0–2.99). Furthermore, the proportion of childhood asthma attributable to the interaction was as high as 47% (AP: 0.47, 95% CI 0.03–0.90).17

The most recent evidence from epidemiologic studies and meta-analyses also show indoor dampness or mold to be consistently associated with increased asthma development and exacerbation, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms—in allergic and nonallergic individuals.16 Studies from China continue to evolve, where the prevalence of both urbanization and childhood asthma have been increasing rapidly.17 Two large epidemiologic studies from China showed that visible mold on walls was significantly associated with physician-diagnosed childhood asthma in both boys and girls.17-19

In the Cincinnati Allergy and Air Pollution Study longitudinal birth cohort, fungal exposure was found to be associated with increased incidence of wheeze in infants and increased risk of developing asthma at age three; it was also a predictor of asthma development at age seven.7 A 2010 meta-analysis of 23 studies suggests that residential dampness and mold are associated with substantial and statistically significant increases both in respiratory infections and bronchitis.20 Dannemiller et al used quantitative PCR (qPCR) and next-generation sequencing (NGS) to analyze archived dust samples collected from the homes of asthmatic children. Asthma severity was associated with the total concentration of fungi analyzed by the qPCR.20,21 In a cohort study in California, exposure to increased daily levels of basidiospores and ascospores (two types of sexual spores produced by fungi) in the first three months of life was associated with increased odds of wheezing among children under 24 months.10,22

Nonrespiratory Conditions

Research in animals and humans on nonrespiratory conditions associated with mold toxicity and DMHS is limited.23 However, some studies and clinical research suggest that physiological dysfunction may be associated with the toxins released in water-damaged buildings, including chronic neurological and immunological diseases.23-28

In humans, autoimmunity of the nervous system may be associated with exposure to fungal bioaerosols from water-damaged homes and buildings.9,29 The authors of a 2010 study investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (numbness, tingling, tremors, and muscle weakness in the extremities). 91 out of 119 (83%) patients in the study presented with peripheral neuropathy, showing significantly higher titers of isotype antibodies (IgA, IgG, and IgM) to neural antigens when compared with 500 healthy controls. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.9,29 This group of patients was also part of another study that demonstrated that mixed mold mycotoxicosis may be implicated in the production of antinuclear autoantibodies and anti-myelin antibodies against the nervous system and autoantibodies against smooth muscles.9,30 The authors propose the term “mixed mold mycotoxicosis” for the multisystem illness observed in these patients.30

In a study of children, both postural tachycardia syndrome (POTS) and myalgic encephalomyelitis or chronic fatigue syndrome (CFS/ME) was common in those exposed to indoor air dampness and mold at schools and/or homes, occurring in 49 out of 81 (60.4%) and 56 out of 81 (69%) of study respondents, respectively.31 The authors speculate that autoantibodies against ?1-adrenergic (?1AR) and ?1/2-adrenergic (?1/2AR) or acetylcholine receptors (AChR) may have played a role in POTS, ME/CFS, and CRPS patients who had been exposed to dampness and mold.31

While research does suggest that mold exposure may be associated with a variety of respiratory conditions and hypersensitivity diseases, many within the scientific community assert that no conclusive medical studies have causally linked mold to nonrespiratory conditions like those mentioned above.32-34 Furthermore, some researchers suspect that toxic mold syndrome or toxic black mold is no more than media hype and mass hysteria, partly stemming from a misinterpreted concept of sick building syndrome—a 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.33 Borchers et al, writing in Clinical Reviews in Allergy & Immunology, say there is no scientific evidence that exposure to visible black mold in apartments and buildings can lead to memory loss, inability to focus, fatigue, and headaches.33 Research on the health effects of mold is ongoing.

Clinical Applications

Patients presenting with a chronic respiratory condition may be evaluated for mold/damp building exposure.5 It may also be pertinent to consider mold toxicity in patients who present with chronic respiratory symptoms or chronic neurological or immunological diseases, particularly those who are not responding to treatment as expected or when all other causes have been ruled out.23

Clinicians assessing for mold toxicity should first determine if the patient has a high likelihood of a condition caused by building dampness.5 Exposure to fungi can be assessed with qualitative and/or quantitative methods.17 Do they spend time in a home or office building with dampness problems? Is mold obviously present in their environment?5 One can also measure the level of humidity or directly measure contaminants in the air, on surfaces, or in dust via four basic methods: culture, nonculture, chemical assays for key toxic molecules, and immunoassays.5

Addressing the root cause begins with decreasing exposure.5 If the foundational cause is excessive building humidity from poor design or water damage, inadequate ventilation, or contaminated air conditioning vents, these issues may require professional assistance.5 A 2013 review paper evaluating eight studies and 6,538 participants found moderate evidence in adults that repairing houses decreased asthma-related symptoms (odds ratio [OR], 0.64) and respiratory infections (OR, 0.57). For children, they reported moderate-quality evidence for reduction of the number of acute care visits (mean difference, -0.45).5,35

The CDC has a wealth of information for patients on how to reduce exposure to mold in the home, as well as information for clinicians helping patients with asthma, allergies, or other respiratory conditions following a hurricane or other tropical storm.

An individual’s ability to detoxify or biotransform and excrete toxic substances is of critical importance to overall health. While the concept that toxins accumulate in the body and are the cause of various health problems has long been a fundamental tenet of traditional healthcare systems around the world, scientists have learned a great deal in recent years about how toxins affect the human population, where they originate, and how to improve the ability to detoxify in a toxic world. Understanding toxicity, including mold and mycotoxin toxicity, and taking practical steps to improve biotransformation are essential and critical pieces in any integrative approach to patient health and well-being.

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