Texas Medical Association's Council on Scientific Affairs - Report on Black Mold and Human Illness

[Guest guest]

: > REPORT OF COUNCIL ON SCIENTIFIC AFFAIRS

: >

: > CSA Report 1-I-02

: > Subject: Black Mold and Human Illness

: > Presented by: O. Edwin McClusky, MD, Chair

: >

: > Over the past several years, increasing public attention has focused on

a

: > potential or suspected role in human illness from the mold Stachybotrys

: > chartarum, commonly known as " black mold, " particularly in association

: > with water-damaged buildings. In Texas, this attention has been manifest

: > not in scientific or medical publications, but rather in the lay press

and

: > in an increasing number of insurance claims filed for mold remediation

of

: > homes and workplaces. Texas Medical Association's Council on Scientific

: > Affairs has been asked to update the " state of the medical science " in

: > this important area.

: >

: > To study this issue, the council conducted a search of medical and

: > scientific literature and contacted Texas and national

: > experts/specialists. After reviewing available data, the council has

: > concluded that public concern for adverse health effects from inhalation

: > of Stachybotrys spores in water-damaged buildings is generally not

: > supported by published reports in medical literature.

: >

: > Recommendation: Approval of the attached policy paper on black mold and

: > human illness.

: >

: > Related 2002-03 Strategic Priority: Expend political capital to promote

: > and strengthen Texas' public health infrastructure.

: >

: > HOUSE ACTION: Approved conclusions and recommendations as policy; filed

remainder of report.

: > BLACK MOLD AND HUMAN ILLNESS

: > SEPTEMBER 2002

: >

: > INTERACTIONS OF HUMANS WITH AGENTS IN THEIR ENVIRONMENT

: >

: > Living organisms capable of causing infection or other types of

illnesses

: > are everywhere in our environment. In addition to molds and other fungi,

: > these include bacteria, viruses, protozoa, and helminthes. Infections

are

: > by far the most common forms of human illness produced by exposure to

: > these organisms. These are generally combated or prevented by our

natural

: > host defenses, which include protein antibodies and cell-mediated

: > immunity. In recent times, anti-microbial drugs have substantially

: > augmented these natural defenses against environmental agents.

: >

: > The human immune and inflammatory systems protect us from a multitude of

: > these and other agents in our environment, usually by one or more of the

: > following four general types of immune reactions: 1

: >

: > 1. Type I reactions are mediated by IgE antibodies and are the cause of

: > most " allergic " reactions. Approximately 8 to10 percent of the

population

: > have adverse symptoms due to Type I reactions to pollens, dust, mold,

: > animal dander, or food.

: > 2. Type II (cytotoxic) reactions target molecules on the surface of

: > cells and initiate processes leading to the death of that specific cell

: > (hemolytic anemia).

: > 3. Type III reactions are " immune-complex " reactions in which a

: > protective antibody attaches to an antigen and initiates an inflammatory

: > reaction (glomerulonephritis).

: > 4. Type IV reactions (cell-mediated immunity) is important in immunity

: > to foreign tissues (organ transplantation), certain infectious agents

: > (tuberculosis), chemicals (contact dermatitis), and in cancer biology.

: >

: > Once specificity is provided by the immune system, effector systems are

: > responsible for neutralization or eradication of the environmental

agent.

: > This is accomplished by inflammatory cells, cytokines, and other

chemical

: > mediators.

: >

: > Still, a minority of persons develop an illness or other adverse

: > manifestation from contact with environmental agents. These adverse

: > effects might take the form of allergies or other immune reactions, or

: > autoimmunity. Autoimmunity, for which there are clear genetic and other

: > factors, is generally thought to be caused by failure of the immune

system

: > to recognize parts of the body as " self. "

: >

: > POTENTIAL HEALTH ISSUES RELATED TO MOLD EXPOSURE

: >

: > In theory, there are five ways in which molds could produce or aggravate

: > human illness or otherwise contribute to symptoms:

: >

: > 1. Type I immune reactions, which can lead to allergic rhinitis (nasal

: > discharge, sneezing, conjunctivitis) or asthma (bronchospasm, wheezing,

: > mucous secretion and plugging).

: > 2. Irritation to mucous membranes through mold production of volatile

: > organic compounds (VOCs) in a manner analogous to non-mold irritants,

: > e.g., tobacco smoke, gas/kerosene stove emissions, ozone.

: > 3. Type III immune reaction, examples including hypersensitivity

: > pneumonitis, which includes " farmer's lung " (lung tissue inflammation

: > occurring from exposure of an inhaled antigen), and allergic

aspergillosis

: > (a rare lung tissue inflammation involving both airways and tissues in

the

: > lungs).3

: > 4. Toxic reaction from mold products (mycotoxins).

: > 5. Toxic reaction from microbial byproducts (endotoxins).4

: >

: > Infectious health issues related to mold exposure can occur in both

normal

: > and immuno-compromised individuals. Normal persons may experience the

: > overgrowth of candida normally found in vaginal and oral cavities after

: > treatment with antimicrobial drugs that alter the dominant normal

: > microbial flora. Another example is chronic dermatophyte infection of

skin

: > (athlete's foot) or nails. Immunocompromised individuals often have true

: > infections with tissue damage when microbes that may be present in the

: > body or environment overgrow and invade body tissues. Examples include

: > re-activation of tuberculosis, histoplasmosis, coccidiomycosis, and

: > invasive candidiasis.

: >

: > The prior reported occasional syndromes associated with residential

fungal

: > exposure primarily have been hypersensitivity pneumonitis.5-10 Human

: > colonization by other environmental fungi also has been reported to

cause

: > chronic allergic sinusitis.11 The cases of hypersensitivity pneumonia

: > reports are case reports; only one has described Stachybotrys as the

: > causal agent.5

: >

: > Ingestion of mycotoxins in foods has been of concern for some time, and

: > there are widespread efforts to protect our food supplies from such

: > agents. Inhalation exposure outside of agricultural or industrial

settings

: > has been thought to be insufficient to produce much morbidity.12

: >

: > Several molds commonly found in homes, including Stachybotrys, are

capable

: > of producing mycotoxins. In vitro (laboratory only), some mycotoxins are

: > capable of blunting the phagocytic removal of particulate matter. Our

: > knowledge about mycotoxins is very incomplete regarding dose-health

: > effects relationships, how to measure them in environmental samples, or

to

: > detect them in patient samples.12

: >

: > STACHYBOTRYS LITERATURE SUMMARY

: >

: > A summary of available literature on Stachybotrys reveals that it is

: > commonly found in water-damaged buildings and dwellings, as are many

other

: > molds. However, there is no convincing evidence that Stachybotrys is a

: > significant or even proven pathogenic antigen in either traditional

: > allergic reactions (Type I hypersensitivity) or the rare forms of

: > hypersensitivity pneumonitis (Type III hypersensitivity). The only

report

: > in the peer-reviewed medical literature suggesting a potentially

: > significant causative role for Stachybotrys in human illness is a report

: > of pulmonary hemorrhage in infants thought to be (but not proven to be)

: > caused by Stachybotrys mycotoxin. Re-examination of this presumed

outbreak

: > has identified shortcomings in the implementation and reporting of the

: > investigation. These reviews have " led CDC to conclude that a possible

: > association between acute pulmonary hemorrhage/hemosiderosis in infants

: > and exposure to molds, specifically Stachybotrys chartarum, commonly

: > referred to by its synonym Stachybotrys atra, was not proven. " 13 The

: > original report was based on suggestive epidemiological evidence rather

: > than proof.14

: >

: > The " state of the science " is perhaps best expressed by Dearborn in his

: > paper " Health Effects of Molds and Mycotoxins " at the 55th Annual

Meeting

: > of the American Academy of Allergy and Immunology, March 2002.12

: >

: > There are major limitations to our better understanding of the potential

: > health impact of chronic toxigenic mold exposure. The exposures are to

: > multiple fungi with varied amounts and types of mycotoxins. Most of the

: > symptoms are rather subjective and difficult to objectively measure.

While

: > quantitative identification of fungi in indoor environments is

improving,

: > quantification of even some of the mycotoxins is at best expensive.

: > Epidemiologic studies are greatly hampered by the lack of either acute

or

: > chronic biomarkers of exposure. Controversy, overreaction, and

inadequate

: > public health prudence will continue until these challenges are

adequately

: > addressed.

: >

: > Terr expressed a similar opinion in a review that examined and critiqued

: > the published literature on Stachybotrys. This review found Stachybotrys

: > to be a minor component of the indoor mycoflora, found on certain

building

: > material surfaces in water-damaged buildings. However, airborne spores

are

: > present in such low concentrations that they are unlikely to cause

: > illness. 15

: >

: > Page and Trout reported in 1998 on a MEDLINE search strategy that

located

: > 13 articles on fungi, mycotoxins, and the indoor environment. They

: > concluded that the literature contained inadequate evidence to support a

: > causal relationship between symptoms or illness among building occupants

: > and exposure to mycotoxins. They recommended, " that research involving

the

: > identification and isolation of specific fungal toxins in the

environment

: > and in humans is needed before a more definitive link between health

: > outcomes and mycotoxins can be made. " 16

: >

: > In summary, the hypothesis that exposure to molds and their toxic

products

: > may lead to adverse health effects can be made. However, the proposition

: > that molds in indoor environments may lead to adverse health effects

: > through mechanisms other than infection and allergic/immunologic

reactions

: > is an untested impression.

: >

: > EVIDENCE REQUIRED TO VALIDATE AN ENVIRONMENTAL AGENT AS CONTRIBUTORY TO

: > HUMAN ILLNESS

: >

: > Koch's postulates are one method to test the concept that molds in the

: > indoor environment may be health hazards. Formulated in 1882, the

: > postulates remain the standard of proof for infectious or toxic agents

and

: > would be the logical and favored form of proof of causation of human

: > illness by Stachybotrys.

: >

: > In short, these postulates hold that:

: >

: > * A pathogenic organism or agent should be associated significantly

: > more often with the illness or syndrome than similar but non-pathogenic

: > organisms;

: > * A pathogenic organism or agent should produce the same or

: > substantially similar pathology in appropriate animal models;

: > * The animal model host must become consistently affected using a

: > natural route (even exposure to a known human pathogen does not

uniformly

: > lead to disease in all humans); and

: > * The return of the suspected causative agent to a human host should

: > produce consistently the features of the illness or syndrome.2

: >

: > Scientific and medical knowledge is built using both direct and indirect

: > evidence. Evidence is indirect if two or more bodies of evidence are

: > required to relate the exposure or intervention of interest to the

: > principal health outcome. More recent methodology has augmented the

: > strength of associations and statistical inferences regarding disease

: > etiology, diagnosis, therapy or interventions, prognosis, and outcomes.3

: > These evidence categories, in decreasing order of validity, include:

: >

: > * Primary studies in humans, particularly large, randomized controlled

: > trials as well as meta-analyses of randomized controlled trials, are

: > recognized as best (small trials are less valid). Nonrandomized

controlled

: > trials, cohort or longitudinal studies, case-control studies, case

series,

: > and reports are less robust, especially the latter two;

: > * Non-human studies (laboratory studies, animal studies); and

: > * Syntheses (systematic reviews).

: >

: > EVALUATING THE ROLE OF STACHYBOTRYS IN " SICK BUILDING SYNDROME "

: >

: > Bernstein has suggested an approach to suspected building-related

illness

: > that includes:17

: >

: > (1) a thorough history (duration and nature of symptoms, home

: > environmental and workplace history, past medical history, family

: > history);

: > (2) a physical exam;

: > (3) exclusion of more common infectious causes;

: > (4) phenotyping the patient as atopic versus non-atopic (skin testing to

: > seasonal and perennial allergens including a mold panel [or

corresponding

: > serologic testing], spirometry pre-/post-bronchodilator);

: > (5) chest x-ray or high-resolution CT of chest (to determine if

: > pulmonary findings consistent with hypersensitivity pneumonitis are

: > present and require additional evaluation);

: > (6) supportive testing including serologic testing for specific IgG,

: > IgE, or IgA to mold (including Stachybotrys), hypersensitivity

pneumonitis

: > screen (precipitating antibodies), and consideration of humoral and

: > cell-mediated immune system evaluation;

: > (7) environmental assessment including walkthrough, air sampling, and

: > measurement of known perennial allergens, irritants (VOCs and chemicals

: > [nitrous dioxide, sulfur dioxide, ozone]), dew point, and mycotoxins;

: > (8) measurement of total symptom scores in and out of the environment;

: > (9) measurement of peak expiratory flow rates in and out of the

: > environment event every 2-3 hours while awake and correlation with

: > environmental exposure measurements; and

: > (10)consideration of specific provocation test (nasal challenge

preferred

: > to the more risky bronchoprovocation).

: >

: > Evidence-based effective interventions for reducing specific types of

: > allergen loads include bedding encasements (dust mites, cat dander,

mold),

: > HEPA filtration (cat and dog dander), HEPA vacuum (cat and dog dander,

: > dust mites, cockroach), dehumidification (<50 percent) with air

: > conditioning or dehumidifiers (dust mites, mold, cockroach), and

thorough

: > cleaning (cockroach).18

: >

: > Other common but less proven methods for reducing allergen loads include

: > air conditioning or other measure to filter outdoor air, removal of

: > carpets, hot (>130o F) washing of bedding, repair of leaky basements,

and

: > changes in home and building design. Patient compliance with these

: > measures usually runs 35 percent or less.18

: >

: > CSA CONCLUSIONS

: >

: > Adverse health effects from inhalation of Stachybotrys spores in

: > water-damaged buildings is not supported by available peer-reviewed

: > reports in medical literature.

: >

: > The probability or possibility of causation or exacerbation of a medical

: > condition due to exposure to mold in indoor environments currently

exists

: > only for the following:

: >

: > * Traditional Type I immune reactions (allergies, with correlation of

: > symptoms with exposure and in vitro demonstration of IgE antibodies by

: > allergy skin tests or RAST test for specific IgE antibodies in blood

: > samples); and

: > * Rare Type III immune reactions (hypersensitivity pneumonitis),

: > pulmonary hemorrhage in infants associated with mycotoxins.

: >

: > Further, for Stachybotrys or other molds to be implicated in other

disease

: > models, the following must be present:

: >

: > * Peer-reviewed medical literature should show clearly that such mold

: > or mold by-product has produced clinical manifestations similar to those

: > displayed by the patient;

: > * Evidence of personal causation of the type described by references

: > 17 and 18 must exist.

: >

: > RECOMMENDATIONS

: >

: > The Council on Scientific Affairs recommends that TMA:

: >

: > (1) support the need for continued scientific research regarding the

: > impact of molds on human health, especially the effects of mycotoxins;

: > (2) educate our membership regarding this issue, including the use of

: > Koch's Postulates as the means to validate illness caused by

Stachybotrys,

: > through information in TMA publications and on the TMA web site;

: > (3) communicate the information in this paper to the appropriate state

: > governmental agencies, such as the Texas Attorney General, Texas

: > Department of Health, Texas Department of Insurance, and others;

: > (4) support that remediation of water damage in homes and other

: > buildings should generally be based on non-clinical factors, unless

clear

: > medical evidence, as described in this paper, exists to demonstrate the

: > role of Stachybotrys in a particular case of illness; and

: > (5) provide educational information on this topic on the TMA web site

: > for interested clinical personnel as well as the general public.

: >

: > OTHER PHYSICIAN REVIEWERS

: >

: > Bonham, MD, Dallas (Otolaryngology)

: > Fawcett, MD, Beaumont (Allergy, Asthma and Immunology)

: > Holcomb, MD, San (Pulmonology)

: > s, MD, San (Allergy, Asthma and Immunology)

: > Bobby Lanier, MD, Fort Worth (Allergy, Asthma and Immunology)

: > Yates, MD, Tyler (Infectious Diseases)

: >

: > REFERENCES

: >

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: > 1997:18-24.

: > 2. Relman DA, Falkow, S. A molecular perspective of microbial

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: > Mandell, , and 's Principles and Practice of Infectious

: > Diseases. Vol. 1. 5th ed. Philadelphia, Pa: Churchill Livingstone;

2000:

: > 9-10.

: > 3. American College of Physicians-American Society of Internal

: > Medicine. Best Evidence 5: Linking Medical Research to Practice [book

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