Adverse Health Effects of Indoor Molds

[Guest guest]

REVIEW

Adverse Health Effects of Indoor Molds

LUKE CURTIS MS, CIH,1 ALLAN LIEBERMAN MD,2 MARTHA STARK

MD,3 WILLIAM REA MD4

AND MARSHA VETTER MD, PHD5

1School of Public Health, University of Illinois at Chicago, Illinois,

2Center for

Occupational and Environmental Health, North ton, South

Carolina, 3Harvard

University, Newton Center, Massachusetts, 4Environmental Health Center,

Dallas,

Texas, 5Environmental Health Center, Hoffman Estates, Illinois, USA

Abstract

Purpose: It has long been known that eating moldy food is hazardous,

and airborne

Aspergillus and other fungi can cause life-threatening illnesses in

immunocompromised

patients. However, the possible health risks of indoor mold exposure in

immunocompetent

humans are controversial. This literature review examines the health

effects of indoor airborne

exposure to mold.

Design: Literature review.

Materials and Methods: This review was conducted by searching PubMed

and other medical

databases, as well as reading recent conference reports.

Results: Many studies link exposure to damp or moldy indoor conditions

to increased

incidence and/or severity of respiratory problems such as asthma,

wheezing and rhinosinusitis.

Stachybotrys produces trichothecenes and other mycotoxins, which can

inhibit protein

synthesis and induce hemorrhaging disorders. Indoor mold exposure can

alter immunological

factors and produce allergic reactions. Several studies have indicated

that indoor mold

exposure can alter brain blood flow, autonomic nerve function, brain

waves and worsen

concentration, attention, balance and memory. Failure to perform the

appropriate objective

evaluations on patients may account for the commonly held belief that

indoor mold exposure

poses no significant health risks to immunocompetent humans.

Conclusions: Exposure to high levels of indoor mold can cause injury to

and dysfunction of

multiple organs and systems, including respiratory, hematological,

immunological, and

neurological systems, in immunocompetent humans.

Keywords: mold, fungi, mycotoxin, allergy, indoor air quality, asthma,

neurotoxicity, lung hemorrhage,

Aspergillus, Penicillium, Cladosporium, Alternaria, Stachybotrys.

INTRODUCTION

In recent years, public attention has become increasingly focused on

human health

concerns linked with mold (fungi) inside homes and workplaces. Indoor

airborne mold

exposure has been associated with adverse human health effects in

multiple organs and

body systems, including respiratory, nervous, immune, hematological and

dermatological

systems. Indoor mold exposure can also lead to life-threatening

systemic infections in

immunocompromised patients.

A qualitative systematic literature review was undertaken in order to

examine and

JNE (gamma) JNE51751.3d 23/11/04 18:04:51 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

Journal of Nutritional & Environmental Medicine (September 2004) 14(3),

1Ð14

ISSN 1359-0847 print/ISSN 1364-6907 online/02/010071-02 # 2004 &

Francis Ltd

DOI: 10.1080/13590840400010318

appraise the current state of knowledge about indoor mold-linked health

effects, and to

summarize the available evidence for the use by health professionals.

Physicians, in

particular, may encounter patients with common symptoms occurring in

particular

environments, and understanding the potential for mold-related health

effects is key to the

complete investigation of those environments. Physicians and industrial

hygienists may be

asked to contribute reports to assist the courts in settling suits. In

2002, an estimated

10,000 mold-related cases were pending in US courts [1]. Also in 2002,

the insurance

industry paid out $2 billion in mold-related claims in Texas alone [2].

Literature was reviewed using the peer-reviewed database, and from

recent conferences

on indoor molds. The levels of evidence available for each topic varied

from level I (from at

least one properly randomized controlled trial) through level II (from

trials without

randomization, exceptionally convincing uncontrolled experiments,

cohort or caseÐcontrol

studies), to level III (opinion of respected authorities based on

clinical experience,

descriptive studies, or reports of expert committees) [3].

MOLDS IN THE INDOOR ENVIRONMENT

Fungi (or molds) are ubiquitous in both indoor and outdoor environments

and are

frequently dispersed by airborne spores. Mold and mold spores require

moisture and a

food source, such as cellulose or decaying food, to grow [4]. As mold

spores swell with

water and grow, they elongate, forming balloon-like protuberances

(hyphae), which secrete

digestive enzymes and mycotoxins. The fungi then digest the food source

to support their

growth.

About 100,000 fungal species have already been identified; in fact,

fungi are estimated to

comprise an astounding 25% of the worldÕs biomass [5]. Various surveys

of homes in North

America and Europe have reported that visible mold and/or water damage

are common,

found in 23Ð98% of all homes examined [6Ð9]. There are no official

standards at this time

for indoor airborne fungi concentrations. However, indoor fungal levels

above a range of

150Ð1000 colony-forming units per cubic meter of air (cfum23) are

considered to be

sufficient to cause human health problems [7, 10Ð12]. Numerous reports

have documented

that indoor air can be contaminated with fungal spore levels well in

excess of 1000 cfum23

[13Ð20]. The most common indoor fungal genera collected are

Cladosporium, Aspergillus

and Penicillium [13Ð20]. Alternaria, Stachybotrys, Rhizopus, Mucor,

Wallemia, Trichoderma,

Chaetonium, yeasts, Botrytis, Epicoccum and Fusarium species are often

found indoors as

well [13Ð20].

MOLD-RELATED HEALTH SYMPTOMS

Patients have been reporting multiple ill health effects linked to

exposures to mold. Studies

of more than 1600 patients suffering ill effects associated with fungal

exposure were

presented at one meeting in Dallas in 2003 (21st Annual Symposium of

Man and His

Environment, Dallas, Texas, 19Ð22 June 2003) [21Ð25].

To cite a few studies: Lieberman [21] examined 48 heavily mold-exposed

patients who

had the following health problems: muscle and/or joint pain (71%),

fatigue/weakness (70%),

neurocognitive dysfunction (67%), sinusitis (65%), headache (65%),

gastrointestinal

problems (58%), shortness of breath (54%),

anxiety/depression/irritability (54%), vision

problems (42%), chest tightness (42%), insomnia (40%), dizziness (38%),

numbness/tingling

(35%), laryngitis (35%), nausea (33%), skin rashes (27%), tremors (25%)

and heart

palpitations (21%). Rea et al.Õs study [23] of 150 heavily indoor

mold-exposed patients

found the following health problems: fatigue (100%), rhinitis (65%),

memory loss and other

neuropsychiatric problems (46%), respiratory problems (40%),

fibromyalgia (29%), irritable

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 2

bowel syndrome (25%), vasculitis (4.7%) and angioedema (4.0%). These

clinical reports

suggest that there can be multisystem adverse effects of airborne mold.

All reported cases

had environmental mold exposure consistent with toxic mold exposure.

MECHANISMS OF MOLD-RELATED HEALTH EFFECTS

Fungi can exert ill health effects by three major mechanisms: allergy,

toxicity, and

infection.

Allergy and Irritation

At least 70 allergens have been well characterized from spores,

vegetative parts and small

particles from fungi (0.3 mm and smaller) [26, 27]. A review of 17

studies revealed that

6Ð10% of the general population and 15Ð50% of atopics had immediate

skin sensitivity to

fungi [28]. Fungi produce beta glucans, which have irritant properties

[29].

Toxicity

Fungi produce a wide variety of toxic chemicals called mycotoxins [4,

30, 31]. Some

common mycotoxins include: aflatoxinsÑvery potent carcinogens and

hepatotoxins,

produced by some Aspergillus species; ochratoxinsÑnephrotoxic and

carcinogenic,

produced by some Aspergillus and Penicillium;

sterigmatocystinÑimmunosuppressive

and a liver carcinogen, produced by Aspergillus species, especially A.

versicolor;

trichothecenesÑproduced primarily by Stachybotrys and Fusarium species

and have

been reported to inhibit protein synthesis and cause hemorrhage and

vomiting. Fungi also

produce beta glucans, which have immunological effects [32]. The smell

of molds comes

primarily from volatile organic compounds [33].

Adverse human and animal effects from mycotoxin-contaminated foodstuffs

have been

well recognized since the early twentieth century [30, 34], but the

pathway of mycotoxin

injury through inhalation is questioned [35]. Because it is unethical

to conduct controlled

studies on humans with inhaled mycotoxin exposure, only controlled

animal exposures and

human cohort and caseÐcontrol studies can be carried out. The

literature reveals that

significant amounts of mycotoxins (including ochratoxin,

sterigmatocystin and trichothecenes)

are present in indoor dust [36Ð39] and dust or fungal particles less

than 10 mm

in diameter are respirable, thus allowing absorption of mycotoxins

through the lungs

[31, 34, 40, 41].

Patients exposed to indoor Stachybotrys have been found to have

measurable blood

levels of the Stachybotrys hemorrhagic toxin stachylysin [42]. Levels

of trichothecene

mycotoxins in urine have also been found in significantly higher levels

in patients exposed

to high indoor fungal levels as opposed to an unexposed control group

[43].

Blood ochratoxin levels have been found to be significantly higher in

food industry

workers exposed to airborne ochratoxin vs. unexposed controls [39].

These findings support

an inhalation pathway for entry of mycotoxins into the body.

Infection

Fungi such as Candida, Histoplasmosis, Cryptococcus, Blastomyces and

Coccidioides can

infect immunocompetent people [44]. Fungi such as Trichophyton, Candida

and Malasezia

commonly cause minor skin infections in immunocompetent humans [45].

Serious infections by such fungi as Candida, Aspergillus and

Pneumocystis mostly involve

severely immunocompromised patients [45Ð47]. In recent years, the

incidence of lifethreatening

infections in immunocompromised patients from Aspergillus and other

common

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

ADVERSE HEALTH EFFECTS OF INDOOR MOLDS 3

fungi has been growing rapidly [48, 49]. Invasive aspergillosis is very

common among

immunocompromised patients, with the following reported incidence

rates: lung

transplants: 17Ð26%; allogenic bone marrow transplants: 5Ð15%; acute

leukemia: 5Ð24%;

heart transplants: 2Ð13% [50Ð51]. Even with strong anti-fungal drugs

and intense hospital

treatment, mortality rates from invasive aspergillosis range from 50 to

99% in the

immunocompromised [52, 53].

SAMPLING FOR MOLD EXPOSURE

Indoor fungal sampling is most commonly performed by measuring airborne

levels of

viable (culturable) or total (viable and non-viable) spores [54, 55].

Some of the airborne

viable sampling methods, such as Andersen samplers, collect air for

only a few minutes.

Settle plates are an inexpensive method to obtain a semi-quantitative

measure of indoor

airborne fungi levels. Viable and non-viable airborne spore counts can

vary considerably

over a period of minutes, so air sampling over several periods of time

may be necessary to

accurately characterize airborne fungal spore levels [54, 55]. However,

airborne fungi

measurements fail to take into consideration mold contamination in dust

or surfaces (often

visible to the naked eye) and mycotoxins in air, dust and on surfaces

[54, 56]. Therefore,

testing settled dust for fungi and mycotoxins has been recommended [54,

55]. Other

techniques, such as polymerase chain reaction (PCR), enzyme-linked

immunosorbent assay

(ELISA), and measurement of fungal volatile organic compounds,

polysaccharides,

ergosterol and beta glucans, have also been found to be useful in

assaying indoor

environments for molds, their allergens and mycotoxins [54].

INDOOR MOLD EXPOSURE AND HEALTH EFFECTS IN BODY SYSTEMS

Respiratory System

Many epidemiological studies have noted that residential exposure to

molds and/or chronic

dampness can increase asthma/wheezing incidence or morbidity in both

children and adults

[7Ð9, 57Ð70]. Asthma and related conditions are very common in the USA,

with an overall

prevalence of about 5.4% among all age groups and incidences as high as

27% in inner city

children [71]. Studies with infants have reported that higher fungal

exposures are associated

with more wheezing, coughing and respiratory illness [72, 73]. Higher

indoor beta glucan

levels have been associated with significantly higher levels of chest

tightness and joint pain

[74]. Non-industrial occupational mold exposure has been reported to be

associated with

significantly higher levels of asthma, sinusitis, irritated skin and

eyes, and chronic fatigue

[75Ð79]. One study found that patients exposed to high indoor fungal

levels had

significantly lower lung function than unexposed controls [24]. Higher

outdoor fungal

concentrations have been linked to higher asthma death rates [80] and

higher asthma

incidence [81Ð83] in children or young adults. Challenge exposures with

Penicillium and

Alternaria extracts equivalent to high outdoor levels of fungi were

noted to severely lower

lung function in asthmatics [84]. Skin sensitivity to Alternaria has

been linked to much

higher risk (odds ratio 190, 95% confidence interval 6.5Ð6.536,

pv0.0001) of respiratory

arrest [85]. Various epidemiological studies have associated skin

sensitivity to common

indoor fungi and higher asthma incidence or severity [86Ð90] and higher

rates of sinusitis

[91].

Airborne fungal exposure is known to cause bronchopulmonary

aspergillosis and

hypersensitivity pneumonitis, and can cause sinusitis [92, 93]. An

estimated 14% of the US

population suffers from rhinosinusitis and related conditions [94].

Allergic fungal sinusitis

was diagnosed on the basis of fungal growth in nasal secretions and the

presence of allergic

mucin in 93% of 101 consecutive patients undergoing sinus surgery [94].

Another study was

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 4

able to recover and culture fungi from the sinuses of 56% of 45

patients undergoing

endoscopic sinus surgery for chronic rhinosinusitis [95]. A long-term

cohort study of 639

patients with allergic fungal sinusitis demonstrated that remedial

steps taken to reduce

fungal exposure (by utilizing, for example, air filters, ionizers,

moisture control and antimicrobial

nasal sprays) significantly reduced rhinosinusitis and improved nasal

mucosa

morphology [22]. This study concluded that failure to reduce airborne

fungi levels to less

than four per hour on a settle plate failed to resolve the sinusitis

[22]. Although,

historically, anti-fungal drugs have generally not been recommended for

the treatment of

fungal sinusitis [92, 93], recent observational studies have found

beneficial effects of oral

and nasal medication for sinusitis patients [22, 96]. Several studies

have linked residential

exposure to various fungi with hypersensitivity pneumonitis [97Ð99].

Hematological Effects

Exposure to high indoor levels of Stachybotrys, Aspergillus and other

fungi has been

epidemiologically associated with infant lung hemorrhage [100Ð104].

Although questions

were raised after this association was discovered [105], it meets many

epidemiological

criteria for causality [106]. Acute infant pulmonary hemorrhage can be

rapidly fatal; when

the infant survives, lung blood vessel damage is present and deposits

of hemosiderin will

remain in the lung macrophages and can be seen in tissue obtained

during bronchoscopy

[101]. Stachybotrys fungi produce a wide range of trichothecene

mycotoxins (including

satratoxins and T2), several roridin epimers, verrucarin J and B and

hemolysin [31, 103]. A

hemorrhagic protein called stachylysin has been isolated from

Stachybotrys collected from

homes of infants with lung hemorrhage [107, 108] and from serum of

patients with

residential Stachybotrys exposure [42]. It is hypothesized that infants

with their rapidly

growing lungs are more susceptible to the toxic effects of Stachybotrys

mycotoxins [109].

Studies with Stachybotrys-exposed adults have noted a significantly

higher incidence of

health conditions such as wheezing, skin and eye irritation, Õflu-like

symptoms and chronic

fatigue [110]. Stachybotrys has been isolated from the lungs of a child

with pulmonary

hemosiderosis [111].

A case study was presented of 16-month-old twins in a mold-infested

home, one of whom

died of pulmonary hemosiderosis [112]. High levels of trichothecene

mycotoxins were found

in the lungs and liver of the dead infant, while high IgG levels to

Stachybotrys and IgM

levels to satratoxin and trichothecenes were found in the serum of the

surviving infant.

Environmental sampling in the twinsÕ home found high levels of

satratoxin as well as high

levels of spores from Stachybotrys, Aspergillus versicolor and

Penicillium [112].

Immune System

Some studies have reported that indoor fungi-exposed patients have

higher serum levels of

IgG, IgA and IgM antibodies to common fungi, trichothecenes and

satratoxins [113Ð115].

IgG antibodies to nine common indoor fungi were significantly higher in

subjects with

sinusitis vs. non-sinusitis subjects in a moldy school [116]. Other

studies have noted no

significant increases in fungal IgG [117, 118] or fungal IgE [113] in

fungi-exposed patients.

Indoor fungal exposure has been associated with altered levels of T4,

T8 and natural killer

cells and higher levels of autoantibodies [23, 25, 119, 120]. Occupants

of homes with high

Indoor glucan exposure had a lower proportion of cytotoxic t-cells

(CD8zSF61z) and

higher secretion of tumor necrosis factor than occupants of homes with

lower levels of beta

glucans [121]. Studies of animals given such common mycotoxins as

aflatoxins, ochratoxins

and trichothecenes orally showed considerable immune impairment,

including depression

of T cells, B cells and macrophages [122]. Human cell line studies have

also found that

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

ADVERSE HEALTH EFFECTS OF INDOOR MOLDS 5

many mycotoxins can suppress T-cell, B-cell and natural killer cell

activity at serum

concentrations similar to those found in indoor mold-exposed patients

[123].

Central Nervous System

Two case series of 48 and 150 mold-exposed patients found significant

fatigue and

weakness in 70Ð100% of cases, and neurocognitive dysfunction including

memory loss,

irritability, anxiety and depression in over 40% of the patients [21,

23]. Numbness, tingling

and tremor were also found in a significant number of patients [21,

23]. These signs and

symptoms have been described as classic manifestations of neurotoxicity

[124].

A study of 43 mold-exposed patients found that they performed

significantly worse than

202 controls on many neuropsychiatric tests, including balance sway

speed, blinking reflex,

color perception, reaction times and left grip strength (pv0.0001)

[125]. Quantitative

electroencephalogram (qEEG) studies in 182 patients with documented

mold exposure also

noted significant alterations in brain waves, including hypoactivation

of the frontal cortex

and narrowed frequency bands [126]. Higher levels of mold exposure

(longer time in moldinfested

area, presence of Stachybotrys or higher cfum23 air) were associated

with

significantly more abnormal qEEGs as well as significantly worse scores

of concentration

and motor and verbal skills in these 182 patients [126]. A

triple-headed SPECT ; brain scan

revealed neurotoxic patterns in 26 of 30 (87%) mold-exposed patients

[127]. An iriscorder

study of autonomic nervous function in 60 mold-exposed patients found

that 95% had

abnormal autonomic responses of the pupil compared with the population

reference range

[23]. Visual contrast sensitivity studies were often abnormal in indoor

mold-exposed

patients [23]. Additional studies have reported that mold-exposed

patients do significantly

worse on tests of attention, balance, reaction time, verbal recall,

concentration, memory,

and finger tapping compared with the general population reference range

[24, 128, 129].

Most of these patients also experienced many health problems, including

chronic fatigue,

headaches, insomnia and decreased balance, concentration and attention.

Studies of indoor

mold-exposed children and adults found significantly more

neurophysiological abnormalities

vs. controls, including abnormal EEGs and abnormal brainstem, visual and

somatosensory evoked potentials [25, 130, 131].

Lieberman [21] presented a case series of 12 patients who developed

tremors following

documented heavy indoor mold exposure. Numerous articles have reported

domestic dogs

developing tremors following ingestion of moldy food [132Ð134].

Territrem b, a mycotoxin

produced by the common fungus Aspergillus terreus, has been shown to be

an irreversible

binder and inhibitor of acetylcholinesterase [135].

Renal System

It is known that ochratoxin-contaminated food is nephrotoxic [136,

137]. Indoor airborne

exposure to ochratoxin may also be nephrotoxic. In a case report of a

family presenting

with increasing thirst/urination, lethargy, and skin rash, a

considerable amount of

ochratoxin was found in their house dust. The family recovered after

moving to another

home [36].

Reproductive System

The literature suggests a relationship between heavy airborne fungal

exposure and

reproductive dysfunction. sen et al. [138, 139] reported that

airborne mycotoxin

exposures in Norwegian grain farmers was significantly related to

higher rates of preterm

deliveries, late-term miscarriages and higher rates of endometrial and

ovarian

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 6

endocarcinoma. The veterinary literature finds a strong association

between mycotoxtins in

feedstuffs and reproductive problems [140].

Diabetes

There is a great deal of evidence that links environmental factors to

the triggering of type 1

diabetes. Exposure to viruses, bacteria and mycotoxins such as alloxan,

streptozatocin and

L-asparginase has been linked to the development of type 1 diabetes in

animals and

humans [141Ð143]. Lieberman [21] reported that in a single year, five

of his patients

developed type 1 diabetes following documented heavy indoor mold

exposure.

DIAGNOSIS AND MANAGEMENT OF POTENTIALLY MOLD-RELATED

HEALTH PROBLEMS

A careful medical and environmental history is an essential first step

in evaluating a patient

for mold-related health problems [144Ð147]. Particular attention should

be paid to any

history of exposure to visible mold and/or water damage at the home or

workplace.

Environmental sampling for viable spores, total spores, and mycotoxins

in the air and dust

can provide important exposure information. For a helpful overview of

sampling methods,

see references [54, 148, 149]. For an informative guide to the

classification, identification

and biology of common indoor fungi, see reference [4]. Several good

guides exist for the

prevention and remediation of indoor fungi problems [144, 148Ð151].

For patients suspected of having substantial fungal exposure, a battery

of sophisticated

laboratory tests has been developed: a basic metabolic panel to test

for several important

parameters (including electrolytes, blood sugar, liver and kidney

status); measurement of

antibodies to molds and mycotoxins in serum [113, 114]; immune tests

for autoantibodies,

complement, gamma globulins and lymphocyte panels [120]; urine and

blood testing for

mycotoxins [43]; visual contrast sensitivity tests; and pupillometry

and heart rate variation

to assist in the evaluation of autonomic nervous system function. The

use of standard

neuropsychological test batteries [23, 128Ð130], EEG and brain imaging

techniques such as

SPECT and magnetic resonance imaging (MRI) can be very helpful tools in

documenting

neurological damage [25,125, 127, 131, 145]. Pulmonary function tests

are also useful for

patients with respiratory symptoms [24, 124]. Failure to perform

objective evaluations to

access system or organ dysfunction account for the presently accepted

position that

airborne mold exposures have no significant adverse effects [35]. If

end-stage organ damage

is suspected, consultation with a specialist may be useful.

Other common indoor environmental exposures should also be considered

as a potential

source of health problems. Common non-fungal indoor environmental

factors include poor

ventilation, carbon monoxide from faulty heat sources, leaking natural

gas, pesticides,

wood smoke, second-hand tobacco smoke, petrochemicals, such as

cleaners/building

materials/solvents, formaldehyde from outgassing carpets, building

materials, bacteria, and

allergens from the fur, feathers, saliva and excrement of common

household animals such

as cockroaches, dust mites, cats, dogs, mice, rats, caged birds, and

pigeons. Exposure to

ozone, second-hand tobacco smoke, cockroach allergens, formaldehyde,

and viral

infections have been noted to have a synergistic effect with fungal

exposure to worsen

asthma and rhinitis [152Ð156].

The most important part of treatment for mold-exposed patients,

symptomatic or not, is

avoidance of fungal exposure and remediation of mold contamination in

the home and

workplace. Any water leaks and damage from flooded or damp areas should

be rectified

immediately. Non-porous surfaces such as floors and walls that have

visible mold growth

should be cleaned. Porous waterlogged materials like carpet and

furniture should be

discarded. Control of humidity is important to control mold growth. The

use of air

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

ADVERSE HEALTH EFFECTS OF INDOOR MOLDS 7

conditioners and dehumidifiers can significantly reduce summertime

indoor airborne mold

concentrations [13, 157]. HEPA air filters can also significantly

reduce indoor airborne

fungi concentrations [158]. For cleaning severe indoor water or mold

problems, the use of

protective equipment like face masks and/or the use of a professional

remediation firm may

be essential [148Ð151].

Environmental control plays a key role in preventing Aspergillus

infections. Several

studies have linked hospital construction work to increased rates of

invasive aspergillosis

[159Ð162]. Environmental controls such as using HEPA filters, sealing

rooms, regular

cleaning of rooms, and using anti-fungal copper-8-quionolate paint have

been shown to

both significantly reduce airborne levels of Aspergillus and

significantly reduce rates of

invasive aspergillosis in immunocompromised hospital patients [158,

160Ð165]. Other recent

research has indicated that a large number of Aspergillus spores can

spread through water

supplies [166] and that cleaning shower facilities can significantly

lower airborne levels of

Aspergillus [167].

Use of sublingual or fungal immunotherapy by injection has been shown

to be beneficial

to some patients sensitized to common indoor molds such as Alternaria

and Cladosporium

herbarium [168, 169]. Some studies with laboratory animals suggest that

a high-quality diet

with adequate antioxidant vitamins, selenium, phytochemicals,

methionine and total

protein can reduce the harmful effects of food mycotoxins [170, 171].

SUMMARY

There is an accumulated weight of evidence linking indoor airborne mold

and/or

mycotoxin exposures to multisystem adverse human health effects. A

history of new

neurocognitive symptoms occurring in patients soon after heavy mold

exposure,

accompanied by objective neuropsychological findings in such patients,

adds considerably

to the weight of evidence from animal studies, epidemiological

research, and case series.

Health care professionals, building managers, homeowners and the

general public need

to be much more aware of the potential adverse health effects of high

indoor fungal

exposures and the need for proper building construction, maintenance,

and remediation of

dampness to prevent such effects. Potentially mold-related illnesses

need to be considered in

differential diagnoses, and careful exposure histories taken. Prompt

removal from exposure

to fungal contamination remains the treatment of choice, with some

evidence that

immunotherapy and nutritional support are also useful. Indoor airborne

mold particles can

be irritative to the respiratory tract, and fungal spores, antigens,

volatile organic

compounds, and mycotoxins can be absorbed through the respiratory route

to provoke

injury by the mechanisms of allergy, toxicity, and infection.

REFERENCES

[1] Umberger M. The start that upstaged the economy. Chicago Tribune,

13 January 2002, available

at WL 2612028, database ALLNEWS.

[2] Mold claims hit $4 billion in Texas, Insurance Journal, 27 May 2003

(http://insurancejournal.

com).

[3] The Canadian Task Force on the Periodic Health Examination. The

Canadian Guide to Clinical

Preventative Health Care. Ottawa: Supply and Services Canada, 1994.

[4] Samson R, Hoekstra E, Frisvad J, Filtenborg O. Introduction to Food

and Airborne Fungi.

Utrecht: Centraalbureau voor Schimmelcultures, 2000.

[5] JD. Fungi as contaminants of indoor air. Atmos Environ 1992;

26A(12): 2162Ð72.

[6] Presternon DR. Perceived moisture problems in Iowa homes. Technical

note. Forest Products J

1991; 41(6): 47Ð48.

[7] Platt S, C, Hunt S, C. Damp housing, mould growth and

symptomatic health state.

Br Med J 1989; 298: 1673Ð8.

JNE (gamma) JNE51751.3d 23/11/04 18:05:07 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 8

[8] Brunekreef B, Dockery D, Speizer FE. Home dampness and respiratory

morbidity in children.

Am Rev Resp Dis 1989; 140: 1363Ð7.

[9] Dales R, Zwanenburg H, Burnett R, lin C. Respiratory health

effects of home dampness

and molds among Canadian children. Am J Epidemiol 1991; 134(2): 196Ð203.

[10] Etzel R. Indoor air pollutants in homes and schools. Pediatr Clin

North Am 2001; 48(5): 1153Ð65.

[11] Flannigan B, McCabe E, McGarry F. Allergic and toxigenic

microorganisms in houses. J Appl

Bacteriol 1991; 70: 61SÐ73S.

[12] Dhillion M. Current status of mold immunotherapy. Ann Allergy

1991; 66: 385.

[13] Curtis L, Ross M, Persky V et al. Bioaerosol concentrations in the

Quad Cities 1 year after the

1993 Mississippi River floods. Indoor Built Environ 2000; 9: 35Ð43.

[14] Shelton B, Kirkland K, Flanders WD, G. Profiles of airborne

fungi in buildings and

outdoor environments in the United States. Appl Environ Microbiol 2002;

68(4): 1743Ð53.

[15] Ren P, Jankun T, Leaderer B. Comparisons of seasonal fungal

prevalence in indoor and outdoor

air and in house dwellings in one Northeast American county. J Exposure

Anal Environ

Epidemiol 1999; 9: 560Ð8.

[16] Pei-Chih W, Huey-Jen S, Chia-Yin L. Characteristics of indoor and

outdoor airborne fungi at

suburban and urban homes in two seasons. Sci Total Environ 2000; 253:

111Ð8.

[17] Li CS, Kuo YM. Characteristics of airborne microfungi in

subtropical homes. Sci Total Environ

1994; 155(3): 267Ð71.

[18] Ebner E, Hasselwandter K, A. Indoor and outdoor incidence of

airborne fungal allergens

at low and high alpine environments. Mycol Res 1992; 97: 117Ð24.

[19] WR. A volumetric study of winter fungus prevalence in the

air of midwestern homes.

J Allergy Clin Immunol 1976; 57(1): 46Ð55.

[20] Beaumont F, Kauffman HF, Sluiter HJ, DeVries K. A

volumetric-aerobiological study of

seasonal fungus prevalence inside and outside dwellings of asthmatic

patients living in northeast

Netherlands. Ann Allergy 1984; 53(6): 486Ð92.

[21] Lieberman A. Explosion of mold cases in homes, workplaces and

occupational medicine

practices. Presented at the 21st Annual Symposium on Man and His

Environment in Health and

Disease, Dallas, Texas, 19Ð22 June 2003.

[22] Dennis D. Chronic sinusitis: defective T-cells responding to

superantigens, treated by reduction of

fungi in the nose and air. Arch Environ Health 2003; 58(7): 433Ð41.

[23] Rea WJ, Didriksen N, Simon TR, Pan Y, Fenyves EJ, Griffiths B.

Effects of toxic exposure to

molds and mycotoxins in building-related illnesses. Arch Environ Health

2003; 58(7): 399Ð405.

[24] Kilburn KH. Indoor mold exposure associated with neurobehavioral

and pulmonary impairment:

a preliminary report. Arch Environ Health 2003; 58(7): 390Ð8.

[25] A, Thrasher J, Madison R, Vojdani A, Gray M, A.

Neural autoantibodies and

neurophysiologic abnormalities in patients exposed to molds in water

damaged buildings. Arch

Environ Health 2003; 58(8): 464Ð78.

[26] Kurup V, Shen HD, Vijay H. Immunobiology of fungal allergens. Int

Arch Allergy Immunol

2002; 129: 181Ð8.

[27] Gorny RL, Reponen T, Willeke K et al. Fungal fragments as indoor

air contaminants. Appl

Environ Microbiol 2002; 68: 3522Ð31.

[28] Institute of Medicine. Clearing the Air. Asthma and Indoor

Exposures. Institute of Medicine < .

[29] Korpi A, Kasanen JP, Kosma VM, Rylander R, Pasanen AL. Slight

respiratory irritation but not

inflammation in mice exposed to (1w3)-beta-D-glycan aerosols. Mediat

Inflamm 2003; 12(3):

139Ð46.

[30] Etzel R. Mycotoxins. J Am Med Assoc 2002; 287(4): 425Ð7.

[31] Nielsen KF. Mycotoxin production by indoor molds. Fungal Genet

Biol 2003; 39: 103Ð17.

[32] Rylander R. Indoor air-related effects and airborne

(1w3)-beta-D-glucan. Environ Health

Perspect 1999; 107(Supplement 3): 501Ð3.

[33] Wilkins K, Larsen K, Simkus M. Volatile metabolites from mold

growth on building materials

and synthetic media. Chemosphere 2000; 41(3): 437Ð46.

[34] J, Klich M. Mycotoxins. Clin Microbiol Rev 2003; 16(3):

497Ð516.

[35] Hardin B, Kelman B, Saxon A. ACOEM evidence base statement.

Adverse health effects

associated with molds in the indoor environment. J Occup Environ Med

2003; 45(5): 470Ð8.

[36] J, Plattner R, May J, Liska S. The occurrence of

ochratoxin A in dust collected from a

problem household. Mycopathologica 1999; 146(2): 99Ð103.

[37] Smoragiewicz W, Cossette B, Boutard A, Krystyniak K. Trichothecene

mycotoxins in the dust of

ventilation systems in office buildings. Int Arch Occup Environ Health

1993; 65(2): 113Ð7.

[38] Engelhart S, Loock A, Skutlarek D et al. Occurrence of toxigenic

Aspergillus versicolor isolates

and sterigmatocystin in carpet dust from damp indoor environments. Appl

Environ Microbiol

2002; 68(8): 3886Ð90.

[39] Iavacoli I, Brera C, Carelli G, Caputi R, Marinaccio A, Miraglia

M. External and internal dose in

subjects occupationally exposed to ochratoxin A. Int Arch Occup Environ

Health 2002; 75(6): 381Ð6.

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

ADVERSE HEALTH EFFECTS OF INDOOR MOLDS 9

[40] Fischer G, Dott W. Relevance of airborne fungi and their secondary

metabolites for

environmental, occupational and indoor hygiene. Arch Microbiol 2003;

179: 75Ð82.

[41] Sorenson WG. Fungal spores: hazardous to health? Environ Health

Perspect 1999; 107

(Supplement 3): 469Ð72.

[42] Van Emon J, A, Yike I, Vesper S. ELISA measurement of

stachylysin in serum to quantify

human exposures to the indoor mold Stachybotrys charatarum. J Occup

Environ Med 2003; 45:

582Ð91.

[43] Croft W, Jastromski BM, Croft AL, s HA. Clinical confirmation

of trichothecene

mycotoxicosis in patient urine. J Environ Biol 2002; 23(3): 301Ð20.

[44] P, Sarosi G. Community acquired fungal pneumonias. Semin

Resp Infect 1989; 4(1):

56Ð63.

[45] Tierney L, McPhee S, Papadakis M. Current Medical Diagnosis and

Treatment. New York:

Lange Medical Books, 2003.

[46] Nicod L, Pache J, Howarth N. Fungal infections in transplant

recipients. Eur Resp J 2001; 17(1):

133Ð40.

[47] Garber G. An overview of fungal infections. Drugs 2001;

61(Supplement 1): 1Ð12.

[48] Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G,

Huebner K. Trends in

the postmortem epidemiology of invasive fungi at a university hospital.

J Infect 1996; 33:

23Ð32.

[49] Husain S, BD, Munoz P et al. Opportunistic mycelial

fungal infections in organ

transplant recipients: emerging importance of non-Aspergillus fungi.

Clin Infect Dis 2003; 37(2):

221Ð9.

[50] Denning D. Report on a European Science Foundation Workshop on

Invasive Aspergillosis,

21Ð22 October 1998, University of Manchester, Manchester.

[51] Kontoyiannis D, Bodey G. Invasive aspergillosis in 2002: an

update. Eur J Clin Microbiol Infect

Dis 2002; 21: 161Ð72.

[52] Denning D. Therapeutic outcome in invasive aspergillosis. Clin

Infect Dis 1996; 23(3): 608Ð15.

[53] Lin S, Schranz J, Teutsch S. Aspergillosis case-fatality rate:

systemic review of the literature. Clin

Infect Dis 2001; 32(3): 358Ð66.

[54] Pasanen AL. A review: fungal exposure assessment in indoor

environments. Indoor Air 2001; 11:

87Ð98.

[55] Dillon HK, JD, Sorenson WG, Douwes J, s R. Review of

methods applicable to the

assessment of mold exposure in children. Environ Health Perspect 1999;

107(Supplement 3):

473Ð80.

[56] J, Bader H. Detection of Stachybotrys charatarum: the

effectiveness of culturable-air

sampling and other methods. Environ Health 1999; 2000: 9Ð11 = .

[57] Gent J, Ren P, Belanger K et al. Levels of household mold

associated with respiratory symptoms

in the first year of life in a cohort at risk for asthma. Environ

Health Perspect 2002; 110(12):

A781Ð6.

[58] Dales R, Burnett R, Zwanenburg H. Adverse health effects among

adultsÕ exposures to home

dampness and molds. Am Rev Resp Dis 1991; 143: 505Ð9.

[59] Ostro B, Lipsett M, Mann J, Braxton-Owens H, White M. Air

pollution and exacerbation of

asthma in African-American children in Los Angeles. Epidemiology 2001;

12: 200Ð8.

[60] Zock J, Jarvis D, Lucynska G, Sunyer J, Burney P. Housing

characteristics, reported mold

exposure, and asthma in the European Community Respiratory Health

Survey. J Allergy Clin

Immunol 2002; 110(2): 285Ð92.

[61] on I, C, McGill G. Damp housing and asthma: a case

control study. Thorax

1997; 52: 229Ð34.

[62] Verhoeff AP, Van Strien RT, Van Wijnen JH, Brunekreef B. Damp

housing and household

respiratory symptoms: the role of sensitization to dust mites and

molds. Am J Epidemiol 1995;

141: 103Ð10.

[63] Strachan DP, Flannigan B, McCabe E, McGarry F. Quantification of

airborne moulds in the

homes of children with and without wheeze. Thorax 1990; 45: 382Ð7.

[64] Brunekreef B. Damp housing and adult respiratory symptoms. Allergy

1992; 47: 498Ð502.

[65] Waegemaekers M, Van Wageningen N, Brunekreef B, Boleij JS.

Respiratory symptoms in damp

homes. A pilot study. Allergy 1989; 44: 192Ð8.

[66] Jedrychowski W, Flak E. Separate and combined effects of the

indoor and outdoor air quality on

chronic respiratory symptoms adjusted for allergy among preadolescent

children. Int J Occup

Med Environ Health 1998; 11: 19Ð35.

[67] Hu FB, Persky V, Flay BR, J. An epidemiological study

of asthma prevalence and

related factors among young adults. J Asthma 1997; 34(1): 67Ð76.

[68] Jaakkola J, Jaakkola N, Ruotsalainen R. Home dampness and molds as

determinants of

respiratory symptoms and asthma in pre-school children. J Exposure Anal

Environ Epidemiol

1993; 3(Supplement 1): 126Ð42.

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 10

[69] Slezak J, Persky V, Kviz F, Ramakrishnan V, Byers C. Asthma

prevalence and risk factors in

selected Head Start sites in Chicago. J Asthma 1998; 35(2): 203Ð12.

[70] Lee YL, Lin YC, Hsiue TR, Hwang BF, Guo YL. Indoor and outdoor

environmental exposures,

parental atopy and physician diagnosed asthma in Taiwanese

schoolchildren. Pediatrics 2003;

112(5): e389Ð95.

[71] Sly RM. Changing prevalence of allergic rhinitis and asthma. Ann

Allergy Asthma Immunol

1999; 82(3): 233Ð48.

[72] Belanger K, Beckett W, Triche E et al. Symptoms of wheeze and

persistent cough in the first year

of life: associations with indoor allergens, air contaminants, and

maternal history of asthma. Am

J Epidemiol 2003; 158: 195Ð202.

[73] Stark PC, Burge HA, LM, Milton DK, Gold DR. Fungal levels in

the home and lower

respiratory tract illness in the first year of life. Am J Resp Crit

Care Med 2003; 168(2): 232Ð7.

[74] Thorn J, Rylander R. Airways inflammation and glucan in a rowhouse

area. Am J Resp Crit Care

Med 1998; 157: 1798Ð803.

[75] Chao HJ, Schwartz J, Milton DK, Burge HA. The work environment and

workersÕ health in 4

large office buildings. Environ Health Perspect 2003; 111(9): 1242Ð8.

[76] Pirhonen I, Nevalainen A, Husman T. Home dampness, moulds and

their influence on respiratory

infections in Finland. Eur Resp J 1996; 9: 2618Ð22.

[77] Koskinen OM, Husman TM, Meklin TM. The relationship between mould

and moisture

observations in houses and state of health of their occupants. Eur Resp

J 1999; 14: 1363Ð7.

[78] Ruotsalainen R, Jaakola N, Jaakola J. Dampness and molds in

day-care centers as an

occupational health care problem. Int Arch Occup Environ Health 1995;

66: 369Ð74.

[79] Wan GH, Li CS. Dampness and airway inflammation and systemic

conditions in office building

workers. Arch Environ Health 1999; 54: 58Ð63.

[80] Targonski P, Persky V, Ramakrishnan V. Effect of environmental

molds on risk of death from

asthma during the pollen season. J Allergy Clin Immunol 1995; 95(5 Part

1): 955Ð61.

[81] Neas LM, Dockery DW, Burge H, Koutrakis P, Speizer FE. Fungus

spores, air pollutants, and

other determinants of peak expiratory flow rates in children. Am J

Epidemiol 1996; 143(8):

797Ð807.

[82] Delfino RJ, Zeiger RS, Seltzer JM et al. The effect of outdoor

fungal spore concentrations on

daily asthma severity. Environ Health Perspect 1997; 105(6): 622Ð35.

[83] Dales RE, Cakmak S, Judek S et al. Influence of outdoor

aeroallergens on hospitalization for

asthma in Canada. J Allergy Clin Immunol 2004; 113: 303Ð6.

[84] Liccorish K, Novey H, Kozak P, Fairshter R, A. Role of

Alternaria and Penicillium spores

in the pathogenesis of asthma. J Allergy Clin Immunol 1985; 76(6):

819Ð25.

[85] OÕHalloren M, Yungiger J, Offord K et al. Exposure to an

aeroallergen as a possible precipitating

factor in respiratory arrest in young patients with asthma. N Engl J

Med 1991; 324(6): 359Ð63.

[86] Zureik M, Neukirch C, Leynaert B, Laird R, Bousquet J.

Sensitization to airborne moulds and

severity of asthma: cross sectional study from European Community

Respiratory Health Survey.

Br Med J 2002; 325(7361): 411Ð4.

[87] Gergen PJ, Turkeltaub PC. The association of individual allergen

reactivity with respiratory

disease in a national sample: data from the second National Health and

Nutrition Examination

Survey, 1976Ð1980 (NHANES II). J Allergy Clin Immunol 1992; 90(4 Pt 1):

579Ð88.

[88] Tariq SM, s SM, s M, Hakim EM. Sensitization to

Alternaria and Cladosporium

by the age of 4 years. Clin Exp Allergy 1996; 26(7): 794Ð8.

[89] Perzanowski MS, Sporik R, Squillance SP et al. Association of

sensitization to Alternaria

allergens with asthma among school aged children. J Allergy Clin

Immunol 1998; 101(5): 626Ð32.

[90] RP, DiNiccolo R, Fernandez-Caldas E, Seleznick MJ, Lockey

R, Good RA. Allergen

specific IgE levels and mite allergen exposure in children with acute

asthma first seen in an

emergency department and in nonasthmatic control subjects. J Allergy

Clin Immunol 1996; 98(2):

382Ð8.

[91] Lander F, Meyer HW, Norn S. Serum IgE specific to indoor moulds,

measured by basophil

histamine release, is associated with building-related symptoms in damp

buildings. Inflamm Res

2001; 50: 227Ð31.

[92] Schubert M. Medical treatment of allergic fungal sinusitis. Ann

Allergy Asthma Immunol 2000;

85(2): 90Ð101.

[93] Greenberger P. Allergic bronchopulmonary aspergillosis, allergic

fungal sinusitis and hypersensitivity

pneumonitis. Clin Allergy Immunol 2002; 16: 449Ð68.

[94] Ponikau JU, Sherris R, Kern EB. The diagnosis and incidence of

allergic fungal sinusitis. Mayo

Clinic Proc 1999; 74: 877Ð84.

[95] Lebowitz R, Waltzman M, s J, Pearlman A, Tierno P. Isolation

of fungi by standard

laboratory methods in patients with chronic rhinosinusitis.

Laryngoscope 2002; 112(12): 2189Ð91.

[96] Rains BM, Mineck CW. Treatment of allergic fungal sinusitis with

high-dose itraconazole. Am

J Rhinol 2003; 17(1): 1Ð8.

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

ADVERSE HEALTH EFFECTS OF INDOOR MOLDS 11

[97] Apostolakos M, Rossmore H, Beckett W. Hypersensitivity pneumonitis

from ordinary residential

exposures. Environ Health Perspect 2001; 109(9): 979Ð81.

[98] Kita T, Nishi K, Fujimura M et al. A case of hypersensitivity

pneumonitis caused by Humicola

fuscoatra. Respirology 2003; 8: 95Ð8.

[99] Ando M, Yoshida K, Soda K, Araki S. Specific bronchoalveolar

lavage IgA antibody in patients

with summer type hypersensitivity pneumonitis induced by Trichosporon

cutaneum. Annu Rev

Resp Dis 1986; 134: 177Ð9.

[100] Centers for Disease Control (CDC): Pulmonary

hemorrhage/hemosiderosis among infants,

Cleveland, Ohio, 1993Ð6. MMWR 1997; 46: 33Ð5.

[101] Montana E, Etzel R, Allan T, Horgan T, Dearborn D. Environmental

risk factors associated with

pediatric idiopathic pulmonary hemorrhage and hemosiderosis in a

Cleveland community.

Pediatrics 1997; 99: 117Ð24.

[102] Etzel R, Montana E, Sorenson W et al. Acute pulmonary hemorrhage

in infants associated with

exposure to Stachybotrys atra and other fungi. Arch Pediatr Adolesc Med

1998; 152: 757Ð62.

[103] Vesper S, Dearborn D, Yike I, Sorenson W, Haugland R. Hemolysis,

toxicity and randomly

amplified polymorphic DNA analysis of Stachybotrys chartarum strains.

Appl Environ Microbiol

1999; 65(7): 3175Ð81.

[104] Dearborn D, P, Dahms B et al. Clinical profile of 30

infants with acute pulmonary

hemorrhage in Cleveland. Pediatrics 2002; 110(3): 627Ð37.

[105] Center for Disease Control and Prevention (CDC). Update:

Pulmonary hemorrhage/hemosiderosis

among infants, Cleveland, Ohio 1993Ð6. MMWR 2000; 49: 18Ð184 > .

[106] Etzel T. Stachybotrys. Curr Opin Pediatr 2003; 15(1): 103Ð6.

[107] Vesper S, Magnuson M, Dearborn D, Yike I, Haugland R. Initial

characterization of the

hemolysin stachylysin from Stachybotrys chartarum. Infect Immun 2001;

69(2): 912Ð6.

[108] Vesper S, Vesper MJ. Stachylysin may be a cause of hemorrhaging

in humans exposed to

Stachybotrys chartarum. Infect Immun 2002; 70(4): 2065Ð9.

[109] Yike I, Allan T, Sorenson W, Dearborn D. Highly sensitive protein

translation assay for

trichothecene toxicity in airborne particulates: comparison with

cytotoxicity assays. Appl Environ

Microbiol 1999; 65(1): 88Ð94.

[110] Johanning E, Biagini R, Hull D, Morey P, Jarvis B, Landsbergis P.

Health and immunology

study following exposure to toxigenic fungi (Stachybotrys chartarum) in

a water-damaged office

environment. Int Arch Environ Health 1996; 68: 207Ð18.

[111] Elidemir O, Colasurdo G, Rossmann S, Fan L. Isolation of

Stachybotrys from the lung of a child

with pulmonary hemosiderosis. Pediatrics 1999; 104(4 Part1): 964Ð6.

[112] Hooper D. Molecular evaluation for autopsy and clinical tissue in

patients. Presented at the 22nd

Annual Symposium on Man and His Environment in Health and Disease,

Dallas, Texas, 27 June

2004.

[113] Vojdani A, A, Kashanian A, Vojdani E. Antibodies against

molds and mycotoxins

following exposure to toxigenic fungi in water-damaged building. Arch

Environ Health 2003;

58(6): 324Ð36.

[114] Vojdani A, Thrasher J, Madison R, Gray M, Heuser G, A.

Antibodies to molds and

satratoxin individuals in a water-damaged building. Arch Environ Health

2003; 58(7): 421Ð32.

[115] Savilahti R, Uitti J, Laippala P, Hussman T, Reiman M.

Immunoglobulin G antibodies of

children exposed to microorganisms in a water-damaged school. Pediatr

Allergy Immunol 2002;

13(6): 438Ð42.

[116] Patovirta RL, Reiman M, Husman T, Haverinen U, Toivola M,

Nevalainen A. Mould specific

IgG antibodies connected with sinusitis in teachers of a mould damaged

school: a 2 year follow up

study. Int J Occup Med Environ Health 2003; 16(3): 221Ð30.

[117] Taskinen TM, Laitinen S, Nevalainen A et al. Immunoglobulin G

antibodies to moulds in schoolchildren

from moisture problem schools. Allergy 2002; 57(1): 9Ð16.

[118] Malkin R, ez K, Marinovich V, Wilcox T, Wall D, Biagini R.

The relationship between

symptoms and IgG and IgE antibodies in an office environment. Environ

Res 1998; 76(2): 85Ð93.

[119] Dales R, D, White J, Dulberg C, Lazarovitis A. Incidence

of residential fungal

contamination on peripheral blood lymphocyte populations in children.

Arch Environ Health

1998; 53(3): 190Ð5.

[120] Vojdani A. Health effects and immunotoxicology of toxigenic molds

and mycotoxins. Presented

at the 21st International Symposium of Man and His Environment in

Health and Disease, Dallas,

Texas, 20 June 2003.

[121] Beijer L, Thorn J, Rylander R. Mould exposure at home relates to

inflammatory markers in

blood. Eur Resp J 2003; 21(2): 317Ð22.

[122] Bondy G, Pestka J. Immunomodulation by fungal toxins. J Toxicol

Environ Health B 2000; 3(2):

109Ð43.

[123] Berek L, Petri IB, Msterhazy A, Teren J, Molnar J. Effects of

mycotoxins on human immune

functions in vitro. Toxicol In Vitro 2001; 15(1): 25Ð30.

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 12

[124] Singer R. Neurotoxicity Guidebook. New York: Van Nostrand

Reinold, 1990.

[125] Gray M, Kilburn K, Crago R. Molds, mycotoxins and public health:

summary of 195 patients

treated collaboratively. Presented at the American Public Health

Association (APHA) Meeting,

Philadelphia, Pennsylvania, 11 November 2002.

[126] Crago BR, Gray M, L, M, Arnold L, Thrasher J.

Psychological, neuropsychological

and electrocortical effects of mixed mold exposure. Arch Environ Health

2003; 58(8):

452Ð63.

[127] Simon T. NeurotoxicityÑmold exposure versus all causes. Presented

at the 21st Annual

Symposium on Man and His Environment in Health and Disease, Dallas,

Texas, 19Ð22 June

2003.

[128] Gordon W, Johanning E, Haddad L. Cognitive impairment associated

with exposure to toxigenic

fungi. Presented at the 3rd International Conference on Fungi,

Mycotoxins and Bioaerosols,

Saratoga Springs, New York, 23Ð25 September 1998. In: Bioaerosols,

Fungi and Mycotoxins:

Health Effects. Assessments, Prevention and Control. Albany, New York:

Eastern New York

Center for Environmental and Occupational Health, 1999.

[129] Didricksen N. Neurocognitive deficits in individuals exposed to

toxigenic molds. Presented at the

21st Annual Symposium on Man and His Environment in Health and Disease,

Dallas, Texas,

19Ð22 June 2003.

[130] Baldo JV, Ahmad L, Ruff R. Neuropsychological performance of

patients following mold

exposure. Appl Neuropsychol 2002; 9(4): 193Ð202.

[131] Anyanwu E, A, Vojdani A. Neurophysiological effects of

chronic indoor environmental

toxic mold exposure on children. Sci World J 2003; 3(4): 281Ð90.

[132] Boysen SR, Rozanski EA, Chan DL, Grobe TL, Fallon MJ, Rush J.

Tremorgenic mycotoxicosis

in four dogs from a single household. J Am Vet Med Assoc 2002; 221(10):

1441Ð4.

[133] Young DL, Villar D, Carson TL, Ierman PM, RA, Bottoff MR.

Tremorgenic mycotoxin

intoxication with penitrem A and roquefortine in two dogs. J Am Vet Med

Assoc 2002; 222(1):

52Ð3.

[134] Naude TW, OÕBrien OM, Rundberget T, McGregor AD, Roux C, Flaoyen

A. Tremorogenic

neuromycotoxicosis in 2 dogs ascribed to ingestion of penitrem A and

possibly roquefortine in

rice contaminated with Penicillium crustosum. J S Afr Vet Assoc 2002;

73(4): 211Ð5.

[135] Chen JW, Luo YL, Hwang MJ, Peng FC, Ling KH. Territrem B. a

tremorgenic mycotoxin that

inhibits acetylcholinesterase with a noncovalent yet irreversible

binding mechanism. J Biol Chem

1999; 274(49): 34916Ð23.

[136] Krogh P, Hald B, Pedersen J. Occurrence of ochratoxin A and

citrinin in cereals associated with

mycotoxic porcine nephropathy. Acta Path Micro Scand 1973; 81 Sect B:

689Ð95.

[137] Castegnaro M, Plestina R, Dirheimer O, Chernosemsky IN, Barsch H.

Mycotoxins, endemic

nephropathy and urinary tract tumors. IARC Sci Pub 1991; 115: 1Ð340.

[138] sen P, Irgens L, Andersen A, Bye AS, Sundheim L.

Gestational age, birth weight, and

perinatal death among births to Norwegian farmers, 1967Ð1991. Am J

Epidemiol 1997; 146:

329Ð38.

[139] sen P, Andersen A, Irgens L. Hormone-dependent cancer and

adverse reproductive

outcomes in farmers familiesÑeffects of climatic conditions favoring

fungal growth in grain.

Scand J Work Health 2000; 26(4): 331Ð7.

[140] Diekman M, Green M. Mycotoxins and reproduction in domestic

livestock. J Anim Sci 1992; 70:

1615Ð27.

[141] Cotran RS. Robbins Pathologic Basis of Disease, 5th edn. New

York: WB Saunders, 1994, p. 914.

[142] Cheta D. Animal models of type 1 (insulin-dependent) diabetes

mellitus. J Pediatr Endocrinol

Metab 1998; 11(1): 11Ð9.

[143] Hoffmeister PA, Storer BE, JE. Diabetes mellitus in

long-term survivors of pediatric

hematopoietic cell transplantation. J Pediatr Hematol Oncol 2004;

26(2): 81Ð90.

[144] Eggleston PA. Environmental control for fungal allergen exposure.

Curr Allergy Asthma Rep

2003; 3(5): 424Ð9.

[145] Heuser G, Axelrod P, Heuser S. Defining chemical injury: a

diagnostic protocol and profile of

chemically injured civilians, industrial workers and Gulf War veterans.

Int Perspect Public Health

2000; 13: 1Ð16.

[146] Marshall L, Weir E, Abelsohn A, Sanborn MD. Identifying and

managing adverse environmental

effects: 1) taking an exposure history. Can Med Assoc J 2002; 166(8):

1049Ð55.

[147] Dales RE, D, McMullen E. Indoor air quality and health:

validity and determinants of

reported home dampness and molds. Int J Epidemiol 1997; 26: 120Ð4.

[148] Macher J (ed.) Bioaerosols: Assessment and Control. American

Conference of Governmental and

Industrial Hygienists (ACGIH), Cincinnati, Ohio, 1999.

[149] Portnoy JM, CS, Kennedy K. Sampling for indoor fungi. J

Allergy Clin Immunol 2004;

113: 189Ð98.

[150] Institute of Medicine Committee on the Health Effects of Indoor

Allergens: Engineering Control

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

ADVERSE HEALTH EFFECTS OF INDOOR MOLDS 13

Strategies. Allergens: Assessing and Controlling Adverse Health

Effects. Engineering Control

Strategies. Washington, DC: National Academy Press, 1993, 206Ð32.

[151] Institute for Inspection, Cleaning and Restoration. IICRC S520

Standard and reference guide for

professional mold remediation. Vancouver, Washington: IICRC Press, 2003.

[152] Higgins BG, Francis HC, Yates G et al. Environmental exposure to

air pollution and allergens

and peak flow changes. Eur Resp J 2000; 16(1): 61Ð6.

[153] Thorn J, Brisman J, Toren K. Adult-onset asthma is associated

with self-reported mold or

environmental tobacco smoke in the home. Allergy 2001; 56: 287Ð92.

[154] Chen WY, Tseng HI, Wu MT et al. Synergistic effect of multiple

indoor allergen sources on

atopic symptoms in primary school children. Environ Res 2003; 93(1):

1Ð8.

[155] Skoner DP. Viral infection and allergy: lower airway. Allergy

Asthma Proc 2002; 23(4): 229Ð32.

[156] Fireman P. Virus-provoked rhinitis in patients who have

allergies. Allergy Asthma Proc 2002;

23(2): 99Ð102.

[157] Hirsch D, Hirsch R, Kalbfleish S. Effect of central

air-conditioning and meterological factors on

indoor spore counts. J Allergy Clin Immunol 1978; 62(1): 22Ð6.

[158] Sheretz RJ, Belani A, Kramer BS et al. Impact of air filtration

on nosocomial Aspergillus

infections. Am J Med 1987; 83(4): 709Ð18.

[159] Panackal A, Dahlman A, Keil K et al. Outbreak of invasive

aspergillosis among renal transplant

patients. Transplantation 2003; 75(7): 1050Ð3.

[160] Oren I, Haddad N, Finkelstein R, Rowe J. Invasive pulmonary

aspergillosis in neutropenic

patients during hospital construction: before and after

chemoprophylaxis and institution of

HEPA filters. Am J Hematol 2001; 66(4): 257Ð62.

[161] Loo V, Betrand C, Dixon C et al. Control of

construction-associated nosocomial aspergillosis in

an antiquated hematology unit. Infect Control Hosp Epidemiol 1996;

17(6): 360Ð4.

[162] Iwen P, J, EC, Winfield BA, Hinrichs SH. Airborne

fungal spore monitoring in a

protective environment during hospital construction, and correlation

with outbreak of invasive

aspergillosis. Infect Control Hosp Epidemiol 1994; 15(5): 303Ð6.

[163] Hahn T, Cummings K, Michalek AM, Lipman B, Segel B, McCarthy P.

Efficacy of highefficiency

particulate air filtration in preventing aspergillosis in

immunocompromised patients

with hematologic malignancies. Infect Control Hosp Epidemiol 2002;

23(9): 525Ð31.

[164] Cornet M, Levy V, Fleury L et al. Efficacy of prevention by

high-efficiency particulate air

filtration or laminar airflow against Aspergillus airborne

contamination during hospital

renovation. Infect Control Hosp Epidemiol 1999; 20(7): 508Ð13.

[165] Withington S, Chambers ST, Beard ME et al. Invasive aspergillosis

in severely neutropenic

patients over 18 years: impact of intranasal amphotericin B and HEPA

filtration. J Hosp Infect

1998; 38(1): 11Ð8.

[166] isie EJ, Stratton SL, Dignani MC et al. Pathogenic

Aspergillus species recovered from a

hospital water system: a 3 year prospective study. Clin Infect Dis

2002; 34(6): 780Ð9.

[167] isie EJ, Stratton SL, Dignani MC et al. Cleaning patient

shower facilities: a novel approach

to reducing patient exposure to aerosolized Aspergillus species and

other opportunistic molds.

Clin Infect Dis 2002; 35(8): E86Ð8.

[168] Bernardis P, Agnoletto M, Puccinelli P, Parmiani S, Pozzan M.

Injective versus sublingual

immunotherapy in Alternaria tenuis allergic patients. J Invest Allergol

Clin Immunol 1996; 6(1):

55Ð62.

[169] Helbling A, Reimers A. Immunotherapy in fungal allergy. Curr

Allergy Asthma Rep 2003; 3(5):

447Ð53.

[170] Galvano F, Piva A, Ritieni A, Galvano G. Dietary strategies to

counteract the effects of

mycotoxins: a review. J Food Protect 2001; 64(1): 120Ð31.

[171] Atroshi F, Rizzo A, Westermarck, Ali-Vehmas T. Antioxidant

nutrients and mycotoxins.

Toxicology 2002; 180(2): 151Ð67.

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014

L. CURTIS ET AL. 14

AUTHORS QUERIES

Journal: Journal of Nutritional & Environmental Medicine

Title: Adverse Health Effects of Indoor Molds

Authors: L. CURTIS ET AL.

Dear Author

During the preparation of your manuscript for publication, the

questions listed below have

arisen. Please attend to these matters and return this form with your

proof. Many thanks

for your assistance

Query

Reference

Query Remarks

1 SPECT in full please.

2 [28] Year?

3 [56] Volume no?

4 [105] Page nos OK?

JNE (gamma) JNE51751.3d 23/11/04 18:05:08 Rev 7.51n/W (Jan 20 2003)

The worth Group, Wakefield +44(0)1924 369598 101014