The conversation in Australia is slowly changing when it comes to the adverse effects of dampness and mould causing innate immune activation in susceptible individuals. This process takes time. Some of the science around this topic is new, which means even some of those working in the healthcare system are not yet aware of it.
As such, TMSA would like to play a role in educating Australians on this health issue by offering a package of peer-reviewed studies and relevant reports. For those needing to put critical information for their healthcare in the hands of their medical practitioners, this summary of ten relevant studies and three reports (along with TMSA’s own explainer on this topic) can be linked to, printed, or emailed:
We also provide a quick summary of each of these studies and reports below.
Relevant Australian Government and WHO Reports
Commonwealth of Australia. (2018, October). Report on the Inquiry into Biotoxin-related Illnesses in Australia. Retrieved January 30, 2021.
Following federal member of parliament Lucy Wicks falling sick with CIRS in 2015, the Australian Government conducted an inquiry into biotoxin-related illnesses in Australia. The inquiry tabled responses from affected individuals, researchers, indoor environmental professionals, clinicians, and the Department of Health. Following this, a report containing seven recommendations was published. The Australian Government later published how they would respond to each of the recommendations.
Several of the committee’s relevant recommendations were:
1. The Department of Health produce and publish in the short term a fact sheet, and in the medium term undertake further research on the potential health effects of exposure to damp and mould; the prevalence of dampness and mould in the built environment; and advice on the prevention and removal of mould.
[Recommendations 2-4 were concerned with the building/environmental side]
5. The Department of Health conduct a review into the treatment of patients presenting with complex illnesses that are difficult to diagnose such as those with CIRS-like symptoms.
6. The Australian Government commission the National Health and Medical Research Council to conduct research into CIRS-like syndromes with a view to assisting in the diagnosis, treatment and management of patients. Research should also examine any links between mould and biotoxins and complex symptoms most commonly reported as typifying CIRS.
7. The Department of Health, in consultation with patient groups, medical practitioners, and health bodies, develop clinical guidelines for general practitioners for the diagnosis, treatment and management of CIRS-like conditions
National Health and Medical Research Council. (2020, November). Consultation Paper: Biotoxin-related illnesses in Australia–Health and medical research needs. Retrieved January 30, 2021.
As part of the Australian Government’s response to the 2018 Inquiry into Biotoxin-Related Illnesses, the National Health and Medical Research Council (NHMRC) published an initial consultation paper on biotoxin-related illnesses in Australia. The NHMRC will be allocating $2 million of funding as part of a targeted call for research in this area. As part of this consultation paper, they conducted an initial literature review in which they stated:
“While the Committee heard there was insufficient evidence and a lack of consensus in Australia on the potential health impacts of biotoxins associated with mould and water-damaged buildings, a number of predominately international studies have reported a range of possible health effects and point to a growing body of evidence in this area.”
More specifically, they noted in the literature:
“… associations between living in water-damaged buildings and adverse health effects including CIRS-like symptoms. These symptoms can include ongoing fatigue, headaches, pain, eye problems, gastrointestinal tract problems, cognitive symptoms such as ‘brain fog’, skin issues and muscle cramps, amongst others.”
Heseltine, E., & Rosen, J. (Eds.). (2009). WHO guidelines for indoor air quality: dampness and mould.
WHO found sufficient epidemiological evidence across different countries and climates that occupants of damp or mouldy buildings, both houses and public buildings, are at increased risk of respiratory symptoms, respiratory infections and exacerbation of asthma. Some evidence suggests increased risks of allergic rhinitis and asthma.
“There is clinical evidence that exposure to mould and other dampness-related microbial agents increases the risks of rare conditions, such as hypersensitivity pneumonitis, allergic alveolitis, chronic rhinosinusitis and allergic fungal sinusitis”.
“Toxicological evidence obtained in vivo and in vitro supports these findings, showing the occurrence of diverse inflammatory and toxic responses after exposure to microorganisms isolated from damp buildings, including their spores, metabolites and components”.
They also found evidence that damp buildings can suppress immune responses, leading to increased susceptibility to infections.
“The immunosuppressive effects of mycotoxins have been confirmed in experimental animals. Trichothecenes T-2 and deoxynivalenol (vomitoxin) impair immune responses to respiratory virus infection, increasing the severity of infection. Some airborne fungi and bacteria may act as opportunistic human pathogens, causing upper or lower airway, pulmonary and in some cases systemic infectious diseases in immunocompromised people.”
“The acute cytotoxicity of fungal strains in damp buildings has been found to be due to the metabolite profile produced in vitro, although their biological activity may not depend solely on toxin production. Fungal spores appear to have toxic effects other than those that cause the inflammatory reaction.”
Finally, they clearly note immune activation, a category of effect beyond the more established allergy, infection, and toxic effects of exposure to dampness and mould.
“Mechanisms of injury include exposure to β-glucans, toxins, spores, cell fragments and chemicals followed by immune stimulation, suppression and autoimmunity as well as neurotoxic effects.”
Eight Relevant Peer-Reviewed Studies
Harding, C. F., Pytte, C. L., Page, K. G., Ryberg, K. J., Normand, E., Remigio,… Abreu, N. (2020). Mold inhalation causes innate immune activation, neural, cognitive and emotional dysfunction. Brain, Behavior, and Immunity, 87, 218–228.
An elegant double-blind, placebo-controlled trial that showed cause and effect of inhaled mold, with and without mycotoxins. They administered Stachybotrys chartarum spores intranasally to mice using three groups:
- Mice administered a placebo (saline);
- Mice administered Stachybotrys spores; and
- Mice administered Stachybotrys spores denatured of their mycotoxins.
Harding et al found it caused innate immune system activation, neuroinflammation, neural and behavioural problems, systemic inflammation and pain. As per their discussion:
“There is now compelling evidence that mold exposure causes serious multi-system health problems in humans including peripheral immune activation and behavioral dysregulation that implies central effects.”
“… roughly 25% of Americans carry major histocompatibility complex gene variants that make them susceptible to long-term inflammation following mold exposure, including the initiation of autoimmune problems and changes in brain structure/function…”
“Our data document for the first time that exposure to known quantities of both toxic and non-toxic mold spores activated a central neural immune response with concomitant cognitive and emotional dysfunction. In addition, we identified a mechanism, innate immune activation, which aptly explains how mold exposure may cause such a diverse array of problems.”
Related: In 2021 a different group of US researchers (Ladd et al., 2021) found that Aspergillus versicolor inhalation in mice negatively altered gene expression of neuroinflammatory, glial activation, and neurotransmitter pathways.
Dooley, M. & McMahon, S.W. (2020). A comprehensive review of mold research literature from 2011 – 2018. Internal medicine review, 6(1).
This systematic review considered 114 epidemiological studies between 2011 and 2018. The combined total number of participants was 270,454 across 30 countries and 5 continents.
The proposition that inhaled mold, mold fragments, toxins and inflammagens, or other components of the air in WDB, cause single and multi-system illness, is supported by 112 of 114 (98.2%) epidemiological articles published between 2011 and 2018.
Seventy-nine studies (69.2%) had at least one association with an OR or RR ≥2.0 and 98 studies (85.9%) demonstrated an OR
or RR ≥1.5. Two hundred fifty-one individual associations showed an OR or RR ≥2.0, 384 associations had OR or RR ≥1.5 and 460 associations noted OR or RR ≥1.25. All findings met 95% confidence.
Ratnaseelan, A. M., Tsilioni, I., & Theoharides, T. C. (2018). Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes. Clinical Therapeutics, 40(6), 903–917.
This review incorporates 16 prior studies on the adverse effects of inhaled mould and mycotoxins in indoor environments. The authors concluded that individuals exposed to moulds and mycotoxins had “symptoms affecting multiple organs, including the lungs, musculoskeletal system, as well as the central and peripheral nervous systems” and also noted more recent evidence implicating mycotoxins in the “pathogenesis of autism-spectrum disorder”. Depression was another common symptom.
“Individuals exposed to mold report an extensive range of symptoms, including malaise, fatigue, and cognitive impairment, which appear to be related to the duration of exposure.”
“…mold-exposed groups had altered neurologic functioning, including changes in body-balance, blink-reflex latency, visual fields, reaction time, and color discrimination, compared with controls.”
The mechanisms of injury discussed immune effects, specifically those centred around neurological pathways, such as pro-inflammatory responses mediated by cytokines from mast cells in the brain and elsewhere.
Shoemaker, R.C., & House, D.E. (2006). Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicology and teratology, 28(5), 573-88.
Dr Shoemaker’s landmark study of CIRS-WDB, then called Sick Building Syndrome, took 26 patients with visible evidence of water damage and/or amplified fungal growth in their homes. The researchers compared diagnostic markers (symptom clusters, MMP-9, VCS, VEGF, MSH, IgE) against normal values. A subset of those patients (14) were included in a double-blind, placebo-controlled clinical trial that used the intervention of cholestyramine, which improved symptoms and visual-contrast sensitivity in those receiving the active intervention but not the placebo.
“These results supported the confirmatory hypotheses, thereby supporting the general hypothesis that [Sick Building Syndrome] is associated with exposure to [Water-Damaged Buildings].”
Note that numerous studies now suggest dampness and mould play a relevant role in Sick Building Syndrome.
Shoemaker, R.C., House, D.E., & Ryan, J.C. (2013). Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health, 5(3) 2013, 396-401.
Dr Shoemaker and colleagues undertook another clinical trial of 20 patients diagnosed with CIRS-WDB, refractory to previous treatment, using the compounded medication vasoactive intestinal polypeptide (VIP). They found VIP:
- reduced refractory symptoms to equal controls;
- corrected inflammatory parameters C4a, TGF beta-1, VEGF, MMP9;
- corrected oestradiol, testosterone and 25-OH Vitamin D;
- returned pulmonary artery systolic pressure (PASP) during exercise to normal; and
- enhanced quality of life in 100% of trial patients.
“Subsequent identification of correction of T-regulatory cell levels supports the potential role of VIP in both innate and adaptive immune function.”
Daschner A. (2017). An Evolutionary-Based Framework for Analyzing Mold and Dampness-Associated Symptoms in DMHS. Frontiers in immunology, 7, 672.
Valtonen V. (2017). Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria. Frontiers in immunology, 8, 951.
Inflammatory chronic illness due to mould and water-damaged buildings has also been investigated in Finland, where it is labelled as dampness and mold hypersensitivity syndrome (DMHS). Daschner presents a hypothesis where the presented evolutionary analysis seeks for the ultimate causes of the vast array of symptoms in DMHS. Symptoms can be interpreted as induced by direct (toxic) actions of spores, mycotoxins, or other fungal metabolites, or on the other side by the host-initiated response, which aims to counterbalance and fight off potentially deleterious effects or fungal infection. Individual susceptibility of immune reactions can confer an exaggerated response, and magnified symptoms are then explained in terms of immunopathology.
“I show some evidence that symptoms and disease in DMHS are associated with an elevated inflammatory status, but the observed respiratory and extra-respiratory syndromes are elicited by different mechanisms, ranging from IgE-mediated allergy to multisystem, autoimmune phenomena, as well as neurobehavioral components.”
Bredesen D. E. (2016). Inhalational Alzheimer’s disease: an unrecognized – and treatable – epidemic. Aging, 8(2), 304–313.
Bredesen, a notable neurodegenerative researcher, identifies three major sub-groups of patients with Alzheimer’s Disease:
- Type 1 usually possessed the APOE-4 gene and had systemic inflammatory disorders.
- Type 2 also possessed the APOE-4 gene but had typically had hormonal and nutritional deficiencies.
- Type 3 were more often APOE-3/3 and had disorders associated with exposures to toxins, including heavy metals, industrial toxicants, and biotoxins produced by microbial agents in water-damaged buildings.
Type 3 cases often presented at younger ages and without the common family history associated with Alzheimer’s. Symptoms were not so much amnestic as cortical, often characterised by “dyscalculia, aphasia, executive dysfunction, or other cortical deficits”.
Bredesen notes the previous research by R.C. Shoemaker and colleagues in identifying, diagnosing, and treating CIRS, a dysfunction of the innate immune system caused by a genetic inability to produce antibodies to biotoxins. This autoimmune disorder has also been identified by Scandinavian researchers under a different moniker: dampness and mold hypersensitivity syndrome (DMHS).
Based on previous descriptions of Alzheimer’s patients with a similar presentation, Bredesen estimates ten per cent of Alzheimer’s patients might suffer from CIRS, and then suggests why this “potential epidemic may have gone unrecognized to date”, in part due to a lack of broader recognition of CIRS.
“These findings suggest that patients with presentations compatible with type-3 Alzheimer’s disease should be evaluated for CIRS (as well as other toxic exposures, such as mercury and copper).”
Jedrychowski, W., Maugeri, U., Perera, F., Stigter, L., Jankowski, J., Butscher,… Sowa, A. (2011). Cognitive function of 6-year old children exposed to mold-contaminated homes in early postnatal period. Prospective birth cohort study in Poland. Physiology & Behavior, 104(5), 989-995.
This study was part of a broader longitudinal investigation into the health effects of various forms of indoor and outdoor air pollution on infants and children. It sought to examine the potential for mould to affect cognitive development in young children. The researchers followed a cohort of 277 babies born at term in Krakow, Poland, monitoring the presence of “visible mould patches on indoor walls” regularly between gestation and up to age 5. A Wechsler Intelligence Scale for Children (WISC-R) was administered to the children at age six.
The IQ scores of the children were adjusted for known confounders, such as “maternal education, the child’s gender, breastfeeding practices in infancy, the presence of older siblings and the prenatal exposure to lead and environmental tobacco smoke (ETS)”.
Those children exposed to indoor mould in their home for greater than two years tested with IQs an average of 10 points lower than those who had no exposure. Long-term mould exposure tripled the risk of low-IQ scoring. Moreover, the study showed that:
“… the negative effect of indoor molds on children’s IQ was consistent and stable at each level of maternal education, which is a good proxy for maternal cognitive capacity.”
This study provides additional evidence to the relationship between dampness/mould and adverse health effects, but doesn’t prove causality. It should be considered in the context of two similar studies:
- Mustonen et al. (2016). Moisture damage in home associates with systemic inflammation in children. Indoor Air, 26(3), 439-447.
- Casas et al. (2013). Early life exposures to home dampness, pet ownership and farm animal contact and neuropsychological development in 4 year old children: a prospective birth cohort study. International journal of hygiene and environmental health, 216(6), 690–697.
Reponen, T., Seo, S. C., Grimsley, F., Lee, T., Crawford, C., & Grinshpun, S. A. (2007). Fungal fragments in moldy houses: a field study in homes in New Orleans and Southern Ohio. Atmospheric Environment, 41(37), 8140-8149.
Previously, theoretical models of mould inhalation suggested that the number of airborne spores in even water-damaged buildings would not be enough to be harmful. Moreover, several studies “have shown that the concentrations of airborne fungal spores in mould problem buildings are not necessarily higher than in non-problem ones”. Admittedly, previous researchers also did not know what number of spores would be needed, given people who were potentially exposed for long durations, nor which moulds, other micro-organisms or biotoxins might cause health problems.
Prior lab testing had predicted that spore fragments (as opposed to whole spores) might also be relevant to human health effects. These studies recognised that:
- fragments have more surface area to carry mycotoxins than whole spores;
- total exposure might be 500x higher when fragments are included; and
- the number of spores and fragments do not always correlate to each other.
Their results showed that the level of spore fragments was between 1,000x and 1,000,000x higher than the number of whole spores. They also noted that whole spores such as Stachybotrys chartarum can be heavy due to their water weight and settle to the floor quite quickly. Fragments, in comparison, can be ultra-fine (<0.1 μm) and stay in the air far longer.
This study disproves previous earlier theoretical models that suggested exposure levels to mould spores in water-damaged buildings were too low to cause adverse health effects.
“High particle surface area may further facilitate the bioavailability of fungal components after the particles are inhaled into the human lung. Due to their small size, fragments may be able to evade phagocytosis by macrophages, and can be translocated through systemic circulation.”
For a more complete list of the science on this topic, please visit TMSA’s page on The Science of CIRS and The Biotoxin Research Database (Google Sheet). There are also two PubMed lists that have been curated by TMSA, a general list of over 400 studies and a children-specific one of 20 studies.
Wikipedia also discusses the effects of dampness and mould on the innate immune system in humans: