ENVIRONMENTAL CLAIMS JOURNAL 2017, VOL. 0, NO. 0, 1-23 i Routledge https://doi.org/10.1080/10406026.2017.1345521 a Taylor & Francis Group
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Environmental Moisture, Molds, and Asthma—Emerging Fungal Risks in the Context of Climate Change
Robert A. Michaels
RAM TRAC Corporation
ABSTRACT
The trend toward increasing frequency and intensity of storms has exacerbated mold and other moisture-related health problems, and can be extrapolated to the future. Mold growth therefore exhibits increasing significance in the context of changing climate. The decades-old hypothesis of mold causation and/or exacerbation of asthma previously has been deemed unproven, though not rejected. The present investigation assesses the status of this hypothesis within the industrial, regulatory, scientific, medical, and legal communities. To assure accuracy, statements from these communities are quoted. Recent high-level reviews, such as by the National Academy of Sciences Institute of Medicine and the United Nations World Health Organization, have failed to consider literature that was available, and studies postdating NAS IOM and UN WHO reviews have confirmed and augmented available literature. As a result, all nine of the Hill criteria of causation in epidemiology now are satisfied. | conclude that, with exposure of sufficient intensity and duration, some molds can cause asthma and/or exacerbate preexisting asthma, and that the hypothesis indeed has been accorded broad acceptance in the communities considered.
Introduction
Mold (fungal) contamination often occurs in residences, schools, workplaces, and other structures occupied by people. The frequency of occurrence depends upon geography, season, and climate, among other factors. A corollary of the dependency of mold contamination frequency on climate is that evident global climate change (whatever may be the quantitative contribution of civilization to it) may affect the future magnitude of the mold problem. Storms create conditions conducive to eventual mold infestation via rainfall, tidal surges, and flooding by rivers and streams. Recent years have evinced a trend toward increasing frequency and intensity of storms, including extreme events such as Hurricane Katrina in 2005, Irene in 2011, and Sandy in 2012, all attaining extreme energy largely from warmer ocean water in their path. The trend (Matonse and Frei 2012; Trenberth 2007), which can be
CONTACT Robert A. Michaels (xs) ram@ramtrac.com [ex] RAM TRAC Corporation, 3100 Rosendale Road, Schenectady, NY 12309.
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extrapolated to the future, already has exacerbated climate-mediated mold and other moisture-related human health problems (Piccininni 2014; Quest Diagnostics 2011; Reid and Gamble 2009).
Mold growth therefore exhibits increasing public health and economic significance in the context of changing climate (for example: Brown, Denning, Gow et al. 2012; Frazer 2013; Heitman et al. 2011). On Vancouver Island in 2001, for example, porpoise corpses washed up on shore “with yeast-packed lungs,” dogs and cats had difficulty breathing, and cats exhibited weeping holes when infections penetrated their skulls (Frazer 2013). Beginning in 1999, people had started becoming ill with an unknown respiratory infection that sapped energy and caused coughing as well as lung and brain nodules. The infections in all of these species turned out to be fungal, associated with the yeast Cryptococcus gattii. In 2004 the fungus had spread to mainland British Columbia, and by 2006 reached the U.S. Northwest, where more than 100 cases were documented, 25-30 percent of them lethal. One explanation is an increase in the average temperature of Vancouver Island over a forty-year period. Another is a combination of development and tourism.
Of course, not all fungal disease outbreaks are related, or as closely related, to climate change. A recent outbreak of a usually rare fungal disease illustrates that mold infestation can be a serious public health problem whether or not it is linked to climate change or to environmental moisture and its inadequate control. A fungal meningitis outbreak in 2012 was caused by contamination of steroids produced by the New England Compounding Center (NECC, Framingham, Massachusetts). According to the U.S. Centers for Disease Control and Prevention (US CDC), over 14,000 people received injections of NECC’s steroids that may have been contaminated. A black mold of the genus Exserohilum was identified in one medicine lot, and found in numerous patients (CDC reported forty-five patients as of October 19, 2012). Among over approximately 400 cases meeting CDC’s fungal meningitis criteria, twenty-nine deaths had occurred as of November 2, 2012 (US CDC 2012). In this case the link to climate change is more tenuous, though real, relating to the increased challenge and expense of maintaining acceptable manufacturing conditions in warmer and moister environs.
Like all organisms, molds (fungi) require a suitable range of environmental conditions to grow, most notably a suitable temperature, moisture level, and substrate (ACGIH 1999; Block, 1952; CA DHS 2001; NYC DOH 1993, 2000, 2002, 2005; Prezant et al. 2008; Sahakian et al. 2008; University of Connecticut 2004; US CDC 2004; US EPA 2001, 2002). When such conditions exist and are allowed to persist in a residence, mold growth is a foreseeable near-term consequence, because mold spores are ubiquitous in the environment (NYC DOH 2000). Thus, a potential mold inoculum is generally present, and can develop into a mold infestation. Under some circumstances, mold infestation can result in allergic reactions, or progress to fungal infection. Further, molds germinate rapidly when conditions are suitable. In residences, suitable temperatures and substrates are typical because residents tend to regulate temperature within a narrow range (room temperature), and many materials that are almost ubiquitous in residences can be used as substrates capable of
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supporting mold growth. The undersides of wood (such as parquet) floors, for example, may constitute a suitable substrate. Key to preventing residential mold growth, therefore, is moisture control (NYC DOH 2000).
Common black molds of the genus Stachybotrys were recognized early for their toxic effects, and targeted early for remediation to maintain a healthy environment. In 1993 the New York City Department of Health (NYC DOH 1993) Guidelines on Assessment and Remediation of Stachybotrys atra [SA] in Indoor Environments drew the following key conclusion:
SA is generally found on materials with a high cellulose content (such as fiberboard, gypsum board, dust and lint) that become chronically moist or water damaged due to excessive humidity, water leaks, condensation, infiltration, or flooding. Such conditions are often accompanied by multiple mold contaminants and other air quality problems. Areas growing SA or other microbial contaminants must be repaired as rapidly as possible in order to assure a healthy environment.
The problem of residential mold contamination, as indicated above, is broader than Stachybotrys atra. Accordingly, NYC DOH addressed the full universe of molds, first in 2000 (NYC DOH 2000), by issuing and updating Guidelines on Assessment and Remediation of Fungi in Indoor Environments (NYC DOH 1993, 2000, 2002, 2005). Federal advice for reducing mold and mold-associated illness, for example (US EPA 2001, 2002, 2005), and regionally relevant New York City Department of Health guidelines applicable to the real estate industry and beyond for assessing and remediating mold contamination, also have been promulgated. NYC DOH states:
The presence of mold, water damage, or musty odors should be addressed immediately. In all instances, any source(s) of water must be stopped and the extent of water damage determined. Water damaged materials should be dried and repaired. Mold damaged materials should be remediated in accordance with this document. (NYC DOH 2002, Environmental Assessment)
An important concept in addressing mold contamination immediately is that use of chemical biocides is neither required nor recommended because it can be damaging. According to NYC DOH guidelines:
The use of gaseous, vapor-phase, or aerosolized biocides for remedial purposes is not recommended. The use of biocides in this manner can pose health concerns for people in occupied spaces of the building and for people returning to the treated space if used improperly. Furthermore, the effectiveness of these treatments is unproven and does not address the possible health concerns from the presence of the remaining non-viable mold” (NYC DOH 2005, 9).
Mold contamination in residences, schools, workplaces, and other environments is more than a public health problem; it also threatens property in these environments and others. Economic costs of mold contamination are large, as suggested by the size of the remediation industry. Costs include inspecting and remediating property and restoring or replacing possessions.
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The costs are not just monetary but, for example, cultural as illustrated over the past decade as a consequence of opening to tourism the famous caves of Altamira (Cantabria, Spain) and Lascaux (Dordogne, France; see, for example, Martin-Sanchez et al. 2012; and Saiz-Jiminez et al. 2011). Paleolithic (Stone Age) cave dwellers adorned the labyrinthine walls of these caves, now designated World Heritage Sites, with paintings depicting aspects of their lives, today constituting priceless artifacts from humanity’s common ancestors documenting development of our species’ earliest art. Two paintings, titled Wounded Bison (Altamira) and Herd of Horses (Lascaux), were popularized in 2003 by the movie Mona Lisa Smile starring Julia Roberts. Entry of tourists, however, has been associated with entry of fresh air, moisture, and microorganisms. As a result, fungal contamination has occurred at both sites. In Lascaux, the biocide benzalkonium chloride applied between 2001 and 2004 now is reported being used by microorganisms as a carbon and nitrogen source (Saiz-Jimenez et al. 2011). More mundane examples of mold damage to property abound, resulting in economic losses including those associated with the costs of replacing possessions and of restoring structures.
In New York City and beyond, members of the real estate industry are guided to remediate leaks upon discovery, or disclose them to occupants who might be in a position to fix them. The guidelines call for testing for mold contamination promptly upon discovery of persistent moisture in a residential (or school) setting. If such disclosure is not made in a timely manner, the scope of necessary and appropriate remediation ultimately may be increased. In all cases, federal, state, and municipal regulators assume implicitly or explicitly that residential mold contamination can cause or exacerbate diseases, most notably asthma.
Exposure. The rapidity of mold infestation and growth together imply a duration of airborne exposure to mold fragments, spores, and mycotoxins that may be close to the full duration of uncontrolled water entry into a residence. In addition to exposure duration, several factors affect exposure intensity. If water entry continues, it may expand the surface area of moisture damage. Gradually increasing the area of wood floor damage, for example, also is likely to increase the opportunity for molds to grow, and increase their rate of entry of their fragments, spores, and toxins (mycotoxins) into residential breathing air. The scope of necessary remediation likewise may increase with time and inattention to the problem.
Airflow across mold-contaminated areas, such as walls and floors, may be exacerbated by HVAC equipment, which would be expected to increase lofting of mold fragments, spores, and mycotoxins into the breathing air. Even when air handling units are turned off, molds may be lofted into the air by natural airflows, for example when windows are opened. Indeed, no airflow at all is required for spores to be “elated” into the air, as a natural reproductive strategy of many fungi including indoor molds (ACGIH 1999).
The most direct evidence of airborne exposure intensity consists of air sampling and analysis. Inspection for mold contamination, and remediation of its effects, has
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become a sizable industry. Air monitoring alone may be inadequate to characterize residential mold contamination, as it is relatively unlikely to detect some molds, such as the black mold Stachybotrys, even if present. For this reason, surface (lift or bulk) sampling also may be necessary:
Air sampling for SA should not be part of routine assessment. This is because air sampling methods for SA are prone to false negative results and therefore cannot be used to rule out contamination ...when the size of the affected area is small or moderate, decisions about appropriate remediation strategies can be made on the basis of visual inspection and bulk sampling. (NYC DOH 1993, 4)
Risks potentially posed to human health depend upon the duration of exposure and concentrations to which people are exposed. In practice, contaminated spaces may be distinguished from relatively uncontaminated spaces via comparison with controls. Controls should include an indoor space that is not water-damaged, and an outdoor space: “Both indoor and outdoor air samples from nearby areas without signs of contamination should be collected and compared” (NYC DOH 1993, 4).
Methods
Methods for the present assessment included evaluation of toxicological, epidemiological, medical, and other scientific literature reporting health effects exerted by molds. Regulatory agency publications and corporate reports of inspections of residences and schools for mold contamination also were evaluated. The analysis is supported further by reference to published procedures specifically accepted and/or prescribed for mold evaluation and remediation (for example ANSI/IICRC 2008; CA DHS 2001; Hung et al. 2005; NYC DOH 1993, 2000, 2002, 2005, 2008; Prezant et al. 2008; US EPA 2001, 2002). In short, this analysis adopts the methods of technical peer review regarding the issue of mold causation and exacerbation of asthma. Penetration of the asthma causation/exacerbation hypothesis within the scientific, medical, regulatory, and industry communities was evaluated in part via its acceptance as reflected by the public record. Detailed quotation of the public record, constituting the best, most irrefutable representations of public positions, was used to document the degree to which these various communities have embraced the hypothesis, and advanced it to the status of scientific knowledge reflected in regulatory agency rules, industrial know-how, and medical practice.
Findings
Molds are fungi (ACGIH 1999). They reproduce via spores that may be disseminated via airborne transport. Mold spores often are prominent in bioaerosols, especially in indoor environments, in which moisture may promote mold growth. Bioaerosols also may include fragments of macroscopic plants (and animals, such as insects), but microscopic bioaerosol components such as spores are especially significant because
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their airborne concentrations may increase rapidly in step with rapid fungal reproduction rates.
Bioaerosols can evoke rapid response among sensitive people, even outdoors, as was illustrated poignantly by a four-day outdoor music festival featuring the music group Country Thunder that was held near a recently plowed alfalfa field in Queen Creek, Arizona, in April 1997 (Michaels 1998a, 1998b; Michaels and Kleinman 2000). About 40,000 people attended, many (given the dry Arizona location) with preexisting respiratory conditions. On Saturday April 26, day 3 of the festival, a wind lofted fragments of alfalfa and other plant material, including mesquite spores, creating a bioaerosol. Attendees reported to emergency medical stations in droves, overwhelming available facilities. Ambulances quickly saturated the nearest hospital. Patients had to be airlifted to more distant health care facilities. A total of about 300 people were overcome over a short period of time (hours).
In the context of litigation, the degree of acceptance of a scientific assertion is important. Good scientific assertions should lead to good scientific policy, which is policy that is based upon good science. When scientific publications persuade the scientific community, they tend likewise to influence the regulatory community, such as the New York City Department of Health (NYC DOH), whose guidelines are cited (and quoted) herein. Agency guidelines in turn influence affected industries, most notably in the present context, companies that evaluate and/or remediate mold contamination. This generally describes the evolution of a scientific hypothesis from being confirmed, to being accorded the status of scientific knowledge and ultimately being incorporated into regulatory agency rules, industrial know-how, and medical practice including medical textbooks used in training physicians.
Mold remediation industry acceptance of mold association with asthma
I examined several mold inspection reports, of which two addressed the issue of health effects potentially exerted by molds. Both reports adopted common language (boilerplate), indicating acceptance more widely in the mold remediation industry, as follows:
Inhalation of fungal spores, fragments (parts), or metabolites (e.g., mycotoxins and volatile organic compounds) from a wide variety of fungi may lead to or exacerbate immunologic (allergic) reactions, cause toxic effects, or cause infections.
Illnesses can result from both high-level, short-term exposures and lower-level, long-term exposures. The most common symptoms reported from exposures in indoor environments are runny nose, eye irritation, cough, congestion, aggravation of asthma, headache, and fatigue.
In order for humans to be exposed indoors, fungal spores, fragments, or metabolites must be released into the air and inhaled, physically contacted (dermal exposure), or ingested. Whether symptoms develop in people exposed to fungi depends on the nature of the fungal material, the amount of exposure, and the susceptibility of exposed persons. Susceptibility varies with their genetic predisposition (allergic reactions do not always occur in all
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individuals), age, state of health, and concurrent exposures. For these reasons, and because measurements of exposure are not standardized and biological markers of exposure to fungi are largely unknown, it is not possible to determine “safe” or “unsafe” levels of exposure for people.
Regulatory agency acceptance of mold association with asthma
U.S. Environmental Protection Agency. The US EPA has evaluated the issue of mold causation and exacerbation of asthma (for example, US EPA 2005). US EPA also regulates airborne particles under authority of the Clean Air Act and, in doing so, periodically develops criteria documents setting forth scientific evidence supporting regulation. In 1996 US EPA published its Air Quality Criteria for Particulate Matter (US EPA 1996), which addresses (along with much else) the association of bioaerosols including airborne molds (fungi) with asthma:
Association of fungal and pollen spores with exacerbations of asthma and allergic rhinitis is well established (Ayres 1986) and fungal spore levels may be associated with asthma mortality (Targonski et al. 1995). The incidence of many other diseases (e.g., coccidioidomycosis) induced by fungal spores is relatively low, although there is no doubt about the causal organisms (Lacey and Dutkiewicz 1994). The potential for fungal induced diseases is much higher in immunocompromised patients and those with unusually high exposures, such as military personnel. (US EPA 1996, 11-135)
U.S. Department of Housing and Urban Development. US HUD is interested in residential mold infestation (for example, US HUD 2005, 2006):
Research indicates that certain molds can cause a variety of adverse human health effects, including allergic reactions in immune responses (e.g., asthma), infectious disease (e.g., histoplasmosis), and toxic effects (e.g., aflatoxin-induced liver cancer) (ACGIH 1999). Molds are thought to play a role in asthma in several ways. They are known to produce a large number of proteins that are potentially allergenic, and there is sufficient evidence to support associations between fungal allergen exposure and asthma exacerbation and upper respiratory disease. In addition, molds may play a role in asthma via release of irritants that increase potential for sensitization, or release of toxins (mycotoxins) that affect immune response (NAS IOM 2000). Finally, mold toxins can cause direct lung damage leading to pulmonary diseases other than asthma (NAS IOM 2000; US HUD 2006, 1).
New York City Department of Health. Regarding the black mold Stachybotrys atra (SA), now renamed S. chartarum (SC; NYC DOH 2000), NYC DOH states the following:
If SA spores are released into the air, there is potential for allergic, respiratory or immunologic symptoms to develop or become exacerbated. These conditions include: asthma, hypersensitivity pneumonitis, allergic rhinitis, dermatitis, sinusitis and conjunctivitis. It is thought that these diseases are mediated by an immune response to SA (or other environmental agents). Many of the related symptoms are non-specific, but debilitating, such as discomfort, inability to concentrate and fatigue. (NYC DOH 1993, 2)
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Regarding the broader universe of fungi, that is, in addition to Stachybotrys chartarum (SC), NYC DOH (2000) states the following:
Fungi in buildings may cause or exacerbate symptoms of allergies (such as wheezing, chest tightness, shortness of breath, nasal congestion, and eye irritation), especially in persons who have a history of allergic diseases (such as asthma and rhinitis). (NYC DOH 2000, 4;
executive summary, 2.)
Many fungi (e.g., species of Aspergillus, Penicillium, Fusarium, Trichoderma, and Memnoniella) in addition to SC can produce potent mycotoxins, some of which are identical to compounds produced by SC. Mycotoxins are fungal metabolites that have been identified as toxic agents. For this reason, SC cannot be treated as uniquely toxic in indoor environments.
People performing renovations/cleaning of widespread fungal contamination may be at risk for developing Organic Dust Toxic Syndrome (ODTS) or Hypersensitivity Pneumonitis (HP). ODTS may occur after a single heavy exposure to dust contaminated with fungi, and produces flu-like symptoms. It differs from HP in that it is not an immune-mediated disease and does not require repeated exposures to the same causative agent. A variety of biological agents may cause ODTS including common species of fungi. HP may occur after repeated exposures to an allergen, and can result in permanent lung damage.
Fungi can cause allergic reactions. The most common symptoms are runny nose, eye irritation, cough, congestion, and aggravation of asthma. (NYC DOH 2000, 4; introduction, 1)
Scientific community acceptance of mold association with asthma
Scientific literature relates a variety of molds; such as Alternaria, Aspergillus, and Trichophyton, to asthma and/or its exacerbation (see for example: Chaudhary and Marr 2011; Fukushima et al. 2010; Halonen et al. 1997; O'Driscoll et al. 2009; OHollaren et al. 1991; Platts-Mills et al. 1987; Ward et al. 1989; Ward et al. 1999). The peer reviewed toxicological, epidemiological, medical, and other scientific literature reporting health effects exerted by molds is vast, its full scope necessarily beyond the scope of this assessment. Regulatory agency acceptance of health effect causation by molds, however, is based upon a narrowly selected subset of such studies. US EPA (1996), for example, cites Ayres (1986; which in turn cites Salvaggio and Aukrust 1981) regarding exacerbation of asthma and allergic rhinitis, and Targonski et al. (1995) regarding the association of airborne fungal spore levels with asthma mortality.
NYC DOH (1993, 2000, 2002, 2005, 2008) cites Husman (1996) and Levetin (1995) regarding mold causation of allergic reactions, including aggravation of asthma most commonly. NYC DOH cites additional scientific articles associating molds in offices and residences with symptoms such as fatigue, respiratory ailments, and eye irritation: Croft et al. (1986); Dales et al. (1991); DeKoster and Thorne (1995); Hodgson et al. (1998); and Johanning et al. (1996).
Significant progress has been made since publication of the studies cited above, and since reliance upon them by regulators. Allergic and other immunologic respiratory disease was found to be a common consequence of allergic sensitivity to fungi (Hope and Simon 2007). It was found to affect 3.6 percent of the general
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population, and 22-38 percent of asthma patients, who were found to have specific immunoglobulin E (IgE) for indoor and outdoor fungal allergens. Remediating home moisture and mold was found to reduce asthma morbidity in children (Johnson et al. 2009; Kercsmar et al. 2006). Installation of biocidal ultraviolet lights in office ventilation systems was found to improve employees’ health and well-being (Menzies et al. 2003).
In an office building with a history of water damage, respiratory illnesses were related to total levels of fungi measured in floor and chair dusts (Park et al. 2008). The strongest correlation of fungi and respiratory disease was “current asthma with post-occupancy physician diagnosis.” According to the authors, “[o]ur findings extend the 2004 conclusions of the Institute of Medicine (NAS IOM 2004) by showing that mold levels in dust were associated with new-onset asthma in this damp indoor environment”
A recent critical review and synthesis of the literature was published by the United Nations World Health Organization (UN WHO 2009). It states:
This document provides a comprehensive review of the scientific evidence on health problems associated with building moisture and biological agents. The review concludes that the most important effects are increased prevalences of respiratory symptoms, allergies and asthma as well as perturbation of the immunological system. (UN WHO 2009, abstract, IV; emphasis added)
The evidence for associations with measured exposures to fungi or other microorganisms or microbial agents is less consistent, probably due to uncertainties in exposure assessment (see Chapter 2). For one health outcome, asthma exacerbation, we consider the evidence to be sufficient to document an association and almost sufficient to document causality of dampness-related factors. (UN WHO 2009, 70-71).
Progress since the UN WHO report of 2009. As indicated above, UN WHO (2009) found that building moisture and associated biological agents exert effects on the prevalence of health conditions including asthma. Indeed, a careful reading supports causation, but for just one criterion of causation (among nine Hill causation criteria in epidemiology; Hill 1965) that was missing: whether a “biological gradient,’ or dose-response relationship, of the adverse effect (asthma) with exposure to the putative causative agent has been documented. That uncertainty has been eliminated.
Indeed, much of interest and relevance has occurred since UN WHO published its report. Visible mold growth in apartments was correlated with levels of immunoglobulin E (IgE) in preschool children’s blood serum, a response to exposure and, therefore, an indicator of exposure (Hsu et al. 2010). The mold Aspergillus fumigatus was found to enhance mite-induced allergic airway inflammation, demonstrating unambiguously a mechanism for asthma exacerbation (Fukushima et al. 2010). Kennedy et al. (2012) reported that identifying severe asthma cases of fungal origin is important “because treatment with imidazole antifungals can provide significant benefit. Taken together, specific treatment using allergen avoidance, immunotherapy, anti-IgE, or antifungal treatment is an important part of the successful management of severe asthma.’
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Most significantly, Park et al. (2008) reported a dose-response relationship of asthma occurrence with exposure to fungi in a water-damaged office building. This is “most significant,” because the report was published in 2008, but was not cited by UN WHO in 2009, even though UN WHO cited other reports published as recently as 2009. It is “most significant” also because it satisfies the one criterion of causality in epidemiological studies that was missing according to the UN WHO study: a dose-response relationship with exposure. The Park et al. study established a doseresponse relationship between exposure to mold and clinical response to that exposure. Further, a confirmatory next step was taken by Kuna et al. (2011), documenting the effectiveness of allergen-specific immunotherapy (against the fungus Alternaria alternata) at reducing asthma symptoms.
In May 2012 such reports culminated in a guest editorial in the journal Science by three mold investigators (Brown, Denning, and Levitz 2012), who stated:
Over 600 different fungi have been reported to infect humans, ranging from common to fatal infections, including those of the mucosa, skin, hair, and nails, and other ailments including allergies. Even influential international organizations, such as the World Health Organization and the Bill and Melinda Gates Foundation, appear not to fully appreciate the burden imposed by infection with fungi. (emphasis added)
Progress relating to the causation issue was summarized most recently by Mendell et al. (2011) and by Chaudhary and Marr (2011). The latter state:
For decades, fungi have been recognized as associated with asthma and other reactive airway diseases. In contrast to type I-mediated allergies caused by pollen, fungi cause a large number of allergic diseases such as allergic bronchopulmonary mycoses, rhinitis, allergic sinusitis and hypersensitivity pneumonitis. Amongst the fungi, Aspergillus fumigatus is the most prevalent cause of severe pulmonary allergic disease, including allergic bronchopulmonary aspergillosis (ABPA), known to be associated with chronic lung injury and deterioration in pulmonary function in people with chronic asthma and cystic fibrosis (CF). (emphasis added)
The review by Mendell et al. (2011) implicitly accepts the causation hypothesis as true, though it falls short of saying explicitly that it is proved. The demonstration of causation seems to await, according to Mendell et al., resolution of the narrower issue, that “causal links remain unclear.” Also, “consistently positive associations across many study designs, populations, ages, and health outcomes [were obtained, and] dose-response relations with observed dampness and mold often were reported [e. g., Biagini et al. 2006; Cummings et al. 2008; Park et al. 2008; Pekkanen et al. 2007]. Further:
“Evidence from epidemiologic studies and meta-analyses showed indoor dampness or mold to be associated consistently with increased asthma development and exacerbation, current and ever diagnosis of asthma, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms. Associations were found in allergic and non-allergic individuals. Evidence strongly suggested causation of asthma exacerbation in children ... .Thus, prevention and remediation of indoor dampness and mold are likely to reduce health risks, but current evidence does not support
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measuring specific indoor microbiologic factors to guide health-protective actions.” (Mendell et al. 2011; emphasis added)
The above statement clearly differs from questioning the causal relationship, instead saying that accepting it as being true probably will reduce mold-associated illness. Scientific criteria for demonstrating causation of disease by an agent were postu-
lated by Robert Koch and Friedrich Loeffler in 1884, and refined by Koch in 1890. Their modern incarnation consists of nine criteria (“Hill's criteria”) for determining whether observed associations of agents with diseases are “causal vs. casual” (Hill 1965).
1. Strength of association;
2. Consistency, as in a variety of settings and among a variety of groups; Specificity of agent and health outcome; Temporality, that is, exposure to cause must precede effect; Biological gradient, that is, dose-response relationship; Plausibility, that is, the association must make sense biologically;
Coherence, that is, consistency with natural history and biology of agent; Experimental evidence supporting association; and
PNA PY
9. Analogy, that is, examples of similar risk factors and outcomes.
The weight of evidence “should be used to conclude whether an association is or is not likely to be causal” (Marsh 1998). That is, “it is not necessary for all of the above criteria to be met in order for a factor to be considered part of the network of causes ofa disease.” Available literature cited above, however, documents satisfaction ofall nine of the above criteria. Indeed, Table 1 documents NAS IOM and UN WHO acknowledgment of eight of the nine criteria as satisfied; several reports cited above,
Table 1. Mold vs. Asthma, Status of Causation Criteria.
Hill Causation Criteria NAS IOM, 2004 UN WHO, 2009 1 Strength of association, yes yes (increased) 2. Consistency, as ina variety of settings and among a yes yes (increased) variety of groups, 3 Specificity of agent and health outcome, yes(moldvs.asthma yes (mold vs. asthma exacerbation) exacerbation) 4 Temporality, that is, exposure to cause must precede yes yes effect, 5 Biological gradient, that is, dose-response relationship, no no (increased, but still marginal) 6 Plausil 'y, that is, the association must make sense bio yes yes log ically, 7 Coherence, that is, consistency with natural historyand yes yes biology of agent, 8 Experimental evidence supporting association, and yes yes 9 Analogy, that is, examples of similar risk factors and yes (implied, butnot yes (implied, but not outcomes. explicitly applied) explicitly applied)
Hill, A. B. 1965. The environment and disease: Association or causation? Proceedings of the Royal Society of Medicine 58(5):295-300.
NAS IOM. 2004. Damp Indoor Spaces and Health. National Academy of Sciences, Institute of Medicine. Washington, D.C.: National Academies Press.
UN WHO. 2009. WHO Guidelines for Indoor Air Quality: Dampness and Mould. Copenhagen: WHO Regional Office for Europe.
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individually and together, fill in the missing biological gradient, that is, demonstration of a dose-response relationship. The caveat must be applied, that mold species differ, and only some are likely to fulfill the Hill criteria.
Medical community acceptance of mold association with asthma
When a conclusion supporting causation is widely accepted in the scientific and medical research communities, it can be used by medical clinicians. Accordingly, the association of molds in damp indoor spaces with adverse health effects was addressed at a high level within the scientific and medical research communities together in 2004 (NAS IOM 2004). The National Academy of Sciences (NAS) Institute of Medicine (IOM) reported:
“The committee found sufficient evidence of an association between exposure to damp indoor environments and some respiratory health outcomes: upper respiratory tract (nasal and throat) symptoms, cough, wheeze, and asthma symptoms in sensitized asthmatic persons. Epidemiologic studies also indicate that there is sufficient evidence to conclude that the presence of mold (otherwise unspecified) indoors is associated with upper respiratory symptoms, cough, wheeze, asthma symptoms in sensitized asthmatic persons, and hypersensitivity pneumonitis (a relatively rare immune-mediated condition) in susceptible persons.
These conclusions are not applicable to immunocompromised persons, who are at increased risk for fungal colonization or opportunistic infections. (NAS IOM 2004, executive summary, 10; emphasis added).
Expanding upon these conclusions, the American Industrial Hygiene Association’s (AIHA’s) publication (Prezant et al. 2008) titled Recognition, Evaluation, and Control of Indoor Mold more broadly summarizes NAS IOM as follows:
Sufficient epidemiologic study has produced evidence of association between damp environments and asthma symptoms in sensitized persons, cough, upper respiratory (nasal and throat) tract symptoms, and wheeze. Sufficient evidence for association with the presence of mold and other agents of microbial origin for these same health effects was found, with more limited or suggestive evidence for lower respiratory illness in healthy (nonatopic!) children. More limited and suggestive evidence was found for asthma development, labored breathing, and lower respiratory illness in otherwise healthy, nonatopic children in damp environments, and for the same effects with addition of cough, wheeze, and development of hypersensitivity pneumonitis in susceptible persons. (5)
Medical researchers and clinicians evidently accept the causation hypothesis as true. Indeed, this conclusion long ago entered the realm of medical microbiology textbooks. These textbooks are used, for example, in medical schools (see information about Aspergillus, below).
Aspergillus. Spores have been reported to be 2.5 mm in diameter and readily aerosolized by fungal fruiting structures (Prezant et al. 2008). As far back as 1973, medical microbiology textbook content embraced acceptance of the causality of asthma by molds, in particular, Aspergillus:
1 Atopy: Type | allergic reaction, specifically one with strong familial tendencies, caused by allergens such as pollens ...and associated with the Prausnitz-Kiistner (IgE class) antibody (Stedman’ Medical Dictionary, 24th ed., 1982).
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Farmers and others who handle decaying vegetation are often heavily exposed to spores of Aspergillus. Asthma and rhinitis due to [that is, “caused by”] antigens of these spores are common; and under predisposing conditions progressive infection can be established. Such conditions include not only those mentioned above (opportunistic fungi), but also chronic pulmonary diseases with impaired ciliary activity in the bronchi (e.g., bronchiectasis, pulmonary tuberculosis, and bronchial neoplasms).
Most initial infections are pulmonary, following inhalation of spores. These germinate, and hyphae grow and penetrate contiguous tissues by direct invasion. They tend particularly to invade blood vessel walls, producing angiitis and thromboses; severe hemoptysis is conspicuous and life-threatening in pulmonary aspergillosis. Infected emboli may also establish wide-spread metastatic granulomatous lesions in various organs. (Kobayashi 1973, 997; emphasis added)
This early acceptance in medical textbooks of fungal causation of asthma apparently was omitted from consideration in the Fraser case (Fraser v. 301-52 Townhouse Corp. 2009) in 2008, finding failure to meet the 1923 Frye standard (Frye v. United States 1923). In 2012 it likewise was omitted from consideration in the Cornell case (Cornell v. 360 W 51st St. Realty LLC 2012), superseding Fraser.
The information quoted above was published in a highly respected medical microbiology textbook in 1973 (Davis et al. 1973), two years before one of its authors, Renato Dulbecco, was awarded the 1975 Nobel Prize in Physiology or Medicine (with co-recipients David Baltimore and Howard Temin). Dulbecco's death in 2012 was the subject of a retrospective in the journal Science, prepared by David Baltimore (Science 2012). Penetration of research into the realm of textbook content typically indicates two relevant and favorable attributes: importance and widespread acceptance of the findings and conclusions. The information quoted above unambiguously links airborne exposure to spores, specifically of the mold Aspergillus, to causation of asthma. Further, it anticipates by three decades the NAS IOM (2004) statement, quoted above, that immunocompromised individuals:
are at increased risk for fungal colonization or opportunistic infections. (Executive Summary, 9; emphasis added)
Unidentified spores. Mold spores often are difficult to identify, for example in the case of the black mold Stachybotrys chartarum (SC; formerly S. atra, SA). This is one reason why NYC DOH (1993) states:
Air sampling for SA should not be part of routine assessment. This is because air sampling methods for SA are prone to false negative results and therefore cannot be used to rule out contamination ... when the size of the affected area is small or moderate, decisions about appropriate remediation strategies can be made on the basis of visual inspection and bulk sampling. (NYC DOH 1993, 4)
Acceptance in the legal community in New York State
As elsewhere, acceptance or rejection of the asthma causation hypothesis in the legal community depends upon interpretation of observed associations as being causal vs. casual. The legal term of art is general causation, most essentially denoting the ability of an agent to cause a disease. Showing general causation is a necessary condition
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for showing specific causation, essentially that a particular individual (plaintiff) was (or was not) harmed by an agent in question. That is, one cannot sustain the claim of injury (specific causation) from an agent that is incapable of causing it (general causation).
Technical evidence supporting mold causation and exacerbation of respiratory conditions including asthma was revisited in a precedent-setting case in New York State: Cornell v. 360 W. 51st St. Realty, LLC in (2012), narrowing a 2008 decision in the case of Fraser v. 301-52 Townhouse Corp. (2009). The 2012 opinion explicates the Court’s concept of the relationship of causation and association in science. The explication is oversimplified and as a result inaccurate (because even a very strong association actually can be casual rather than causal), but it does indeed accept the causation hypothesis as true:
The results of the studies relied on by plaintiff were found to be statistically significant, meaning the strength of the association was sufficient to conclude, within the range of probability, that exposure to mold caused the identified ill-health effects. Scientists do not report their results in terms of black and white causality, but rather, in terms of the strengths of the associations found. These associations having been found sufficiently strong by the literature as to be indicative of a causal relationship, plaintiff’s evidence must be deemed to meet the Frye (“gatekeeper”) standard.
Discussion and conclusions
Moisture and mold
Conditions for mold growth in moist residences may be ideal, for example under wetted wood parquet floors which, especially if spongy, may provide a high-cellulose substrate for growth. Molds growing on surfaces such as the undersides of wood floors and behind walls may release spores into the water and, even with limited ventilation, into the air. Dissemination of spores by passive air currents may be augmented episodically by operation of air handling equipment such as air conditioners, heaters, and heat pumps. Each air sample taken at a residence may be viewed as a snapshot of conditions at the time and location of the sample. Fluctuations would be captured better by a movie than by a snapshot. Yet, presumably, seemingly static conditions suggested by analysis of air sample snapshots actually fluctuate with inevitable variations in air currents.
A trend toward increasing airborne concentrations of mold spores (as well as mold fragments and mycotoxins) may be superimposed upon such random airflow fluctuations. Indeed, fungal growth may continue. Airborne concentrations of mold spores, mold fragments (Gorny et al. 2002), and mycotoxins may increase, as long as moisture, nutrients, and other environmental conditions remain suitable, that is (most notably), until remediation activities cut off moisture essential for continued fungal growth.
Asthma and mold
Findings made herein affect the status of scientific knowledge of the role of bioaerosols including mold fragments (Gorny et al. 2002), viable spores, and
ENVIRONMENTAL MOISTURE, MOLDS, AND ASTHMA © 15
organic mycotoxins in causing asthma and/or exacerbating preexisting asthma among people chronically exposed in their indoor breathing air. This aspect of the causation issue is referred to as general causation. Establishment of general causation constitutes a necessary condition for a physician’s conclusion of specific causation regarding his or her particular patient. As reported in Findings, the association of airborne mold with asthma causation and exacerbation is clear and, as early as 1973, asthma causation by fungal spores was described in a highly regarded medical microbiology text with respect to the mold Aspergillus. The causation finding is even stronger with respect to immunocompromised individuals.
In short, airborne mold spores of some species can cause asthma and exacerbate symptoms of existing asthma. This is the preponderant opinion of the scientific, medical, and regulatory communities as indicated by citations of publications originating from each of these interlinked communities as well as reports by mold remediation companies.
Scenarios for human exposure to airborne toxins typically are complex, a situation that introduces difficulty for epidemiologists seeking to isolate specific unique causes to determine whether they are associated with observed medical conditions. In short, ethical standards preclude use of people as bioassay organisms, whose exposures may be narrowly controlled in an experimental set-up such as cages in a laboratory. As a source of uncertainty regarding causation, the complexity of human exposures may be the most common impediment precluding definitive determination of causation in epidemiology studies in which strong associations are found. In the case of the association of molds with asthma exacerbation, scientific opinion clearly leans toward affirmation; for immunocompromised people, the association is even closer to being demonstrably causative. In this circumstance, the preponderant scientific view is that the association is causative, as reflected by regulatory agency actions embracing this conclusion.
Defendants in lawsuits relating to asthma exacerbation due to failed or inadequate remediation of mold damage have sought judicial requirement of proof that asthma exacerbation was caused by molds ofa particular genus, for example, Penicillium in one case. The suggested requirement to demonstrate asthma exacerbation by any particular species of mold, notwithstanding the many shared properties of bioaerosols containing molds and other plant material, is extreme, much as demanding separate proof that bullets of each caliber could harm people, rather than (more reasonably) accepting the hypothesis based upon consideration of the shared properties of bullets of various calibers. A polar opposite extreme is equally unsatisfactory: that if one mold can be causative, all can. The reality is more complex.
In the case of molds, the scientific basis for establishing the unambiguous association of airborne molds with exacerbation of asthma likewise relates to shared properties of multiple species of molds. This is analogous to structure-activity relationships (SARs) used for extrapolating properties of tested chemicals to untested chemicals that are structurally similar, as in classes of chemicals such as polychlorinated biphenyls (PCBs) and chlorinated dioxins. Molds share the property of releasing airborne spores, mold fragments (Gorny et al. 2002), and mycotoxins (for example Viana 2002). Most notably, properties of these airborne particles include
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being small, inhalable, and allergenic. Further, various species of mold produce the same types of mycotoxins. For example:
Many fungi (e.g., species of Aspergillus, Penicillium, Fusarium, Trichoderma, and Memnoniella) in addition to SC [the black mold, Stachybotrys chartarum] can produce potent mycotoxins, some of which are identical to compounds produced by SC. Mycotoxins are fungal metabolites that have been identified as toxic agents. For this reason, SC cannot be treated as uniquely toxic in indoor environments. (NYC DOH 2000, 4; Introduction, 1)
Indeed, much human disease is associated with a large number of species of fungi, further illustrating the need to recognize, where applicable, their shared pathogenic properties:
Fungi infect billions of people every year, yet their contribution to the global burden of disease is largely unrecognized. Most are “relatively” minor infections, but millions contract diseases that kill at least as many people as tuberculosis or malaria ... the incidence of invasive fungal infections is rising as a result of modern medical interventions and immunosuppressive diseases.
Over 600 different fungi have been reported to infect humans, ranging from common to fatal infections, including those of the mucosa, skin, hair, and nails, and other ailments including allergies. Even influential international organizations, such as the World Health Organization and the Bill and Melinda Gates Foundation, appear not to fully appreciate the burden imposed by infection with fungi. (Brown, Denning, and Levitz 2012)
In scientific and medical research, the burden of proof subtly shifts in response to the weight of evidence. Based upon the above considerations, the preponderance of evidence and opinion from research in health risk assessment holds that some molds can cause asthma or exacerbate existing asthma. A preponderance of evidence is not the same as absolute proof under the stringent research criteria of statistical significance and repeatability. From a practical risk management viewpoint, however, it does indicate that the burden of scientific and medical proof (distinct from legal proof, were the burden typically is the onus of the moving party) has shifted to doubters and deniers.
The research community has been heard clearly by regulatory agencies voting with their feet, so to speak, by embodying this causation conclusion in their guidelines relating to molds and mold remediation. This risk assessment message has spawned an entire risk management industry engaged in remediating mold in residences, schools, and workplaces. In short, regulatory activities reflect judicious application of the precautionary principle, under which proactive steps to prevent illness, even in the face of uncertainty that it will occur in a particular individual, are widely and wisely accepted as being justified.
Causation by mold in the context of research versus litigation
The gold standard of medical and scientific proof in research most fundamentally consists of meeting two criteria: statistical significance (typically 95% confidence) and repeatability. The discussion of causation presented above might fall short of meeting this gold standard, but it does illustrate that the medical and scientific
ENVIRONMENTAL MOISTURE, MOLDS, AND ASTHMA © 7
research communities have accepted the causation argument. It illustrates, too, that the regulatory community has embraced it with guidelines for remediating mold, explicitly justified based upon public health criteria. Further, science itself recognizes limitations of simplistic statistical testing against a confidence limit, such as 95 percent. Indeed, the American Statistical Association recently issued a statement to combat pervasive misunderstanding in the scientific, business, and public policy communities of the 95 percent confidence limit and its routine, often inappropriate application (Goodman 2016). In the context of litigation, the gold standard is more probably than not, (51% confidence) or to a reasonable degree of scientific certainty. Both of these litigation criteria of causation clearly have been met with respect to mold exacerbation of asthma, especially in immunocompromised people.
Alternatives to mold
If any uncertainty exists regarding the generally causal relationship between asthma exacerbation and airborne mold, that uncertainty relates to confounding factors commonly encountered in epidemiology studies. Confounding factors may include moisture in living or working spaces, and resulting infestation with biota other than molds, such as bacteria and insects (such as cockroaches). Any of these could be a proximal cause of asthma exacerbation.
Whether the moisture entering a residence is permissive to infestation with molds, bacteria, cockroaches, or other pests might constitute a distinction without a difference. The common feature of each of these scenarios is that moisture is allowed to enter a residence, resulting in moisture-related health and economic consequences. The potential consequences of inattention to chronic moisture entry into residences is expressed well by UN WHO:
We “conclude that there is sufficient evidence of an association between indoor dampnessrelated factors and a wide range of respiratory health effects ..., including asthma development, asthma exacerbation, current asthma, respiratory infections, upper respiratory tract symptoms, cough, wheeze and dyspnoea. (UN WHO 2009, 77)
The climate change context
Considerations above show that moisture constitutes a common if not ubiquitous confounding factor regarding the issue of potential mold causation of asthma, and/or exacerbation of preexisting asthma. Moisture also may give rise to other confounding factors being present, such as bacteria, cockroaches, and other microbial or insect allergens. Overall, these related factors may trend in the same direction in the context of climate change. Climate is indeed changing. As conditions become warmer, they may increase moisture, insects, and molds. All of these factors may be jointly and individually associated with causation and/or exacerbation of asthma. The complexity of isolating each co-occurring factor, qualitatively and quantitatively, should not detract from the attribution of asthma and/or its exacerbation to each factor, individually and jointly.
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Conclusion
Airborne molds may cause respiratory symptoms in people chronically exposed via inhalation in their homes, schools, or workplaces. Mold contamination associated with chronically uncontrolled moist conditions in human-occupied buildings is a cause or contributor to causing asthma among occupants. Asthma also may be exacerbated in asthmatics exposed to airborne molds. People who have asthma and also are immunocompromised, such as by the autoimmune disease multiple sclerosis (Whitacre et al. 1999), constitute a sensitive subpopulation.
The trend toward increasing frequency and intensity of storms has exacerbated mold and other moisture-related health problems, and can be extrapolated to the future. Mold growth therefore exhibits increasing public health and economic significance in the context of changing climate. The decades-old hypothesis of mold causation and/or exacerbation of asthma repeatedly has been deemed unproven, though not rejected. The present investigation assessed the status of this hypothesis within the industrial, regulatory, scientific, legal, and medical communities. To assure accuracy, statements from these communities were quoted. Recent high-level reviews, such as by the National Academy of Sciences Institute of Medicine and the United Nations World Health Organization, have failed to consider literature that was available, and studies postdating NAS IOM and UN WHO reviews have confirmed and augmented available literature. As a result, all nine of the Hill criteria of causation in epidemiology now are satisfied. I conclude that, with exposure of sufficient intensity and duration, some molds can cause asthma and/or exacerbate preexisting asthma, and that this causation/exacerbation hypothesis indeed has been accorded broad acceptance in the communities considered.
About the author
Dr. Robert A. Michaels (ram@ramtrac.com) is president of Schenectady-based RAM TRAC Corporation, and a toxicologist specializing in assessment and management of risks to public health potentially posed by environmental contaminants. He has served numerous corporate clients, the US. Congressional Office of Technology Assessment, and public interest organizations such as the Natural Resources Defense Council (NRDC). Dr. Michaels chaired the State of Maine Scientific Advisory Panel, and for twenty years chaired the Certification Review Board of the Academy of Board Certified Environmental Professionals (ABCEP); he now serves as an ABCEP trustee. Michaels has been secretary of the National Fire Protection Association (NFPA) Committee on Classification and Properties of Hazardous Chemicals, board member of the National Association of Environmental Professionals, and member of the editorial advisory boards of Springer-Verlag and Cambridge University Press journals.
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Publication citation
Michaels, RA. Environmental moisture, molds, and asthma - emerging fungal risks in the context of climate change. Routledge, Taylor & Francis Group, Environmental Claims Journal, 29(3):171- 93, 2017; online: https://doi.org/10.1080/10406026.2017.1345521, 26 July 2017;