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Airborne Fungi and Mycotoxins
DE-WEI LI, ECKARDT JOHANNING, AND CHIN S. YANG
3.2.5
Fungi are a heterogeneous group of organisms including true
fungi (Kingdom Eumycota or Fungi), lichens (a fungus and
an alga in symbiotic relationship), the true slime molds (Myx-
omycetes, Kingdom Protozoa), and the water molds (Oomy-
cetes, Kingdom Chromista). At present the latter two are
sometimes referred to as fungi-like organisms due to their phy-
logenetic differences from the true fungi. Frequently, they are
still called fungi, since they are traditionally studied by mycol-
ogists and covered in mycology (1). Fungi as a group inhabit a
wide range of niches and environments from plants, plant
debris, soils, and animals to exposed rock (some lichens), riv-
ers and lakes (aquatic fungi), the sea (marine fungi), the
North Pole, and the tropics (2). They have developed
many different modes of obtaining nutrients. Fungi function
in both beneficial and detrimental ways from a human per-
spective. Some fungi, such as powdery mildews and rusts,
are obligate parasites of plants. Some fungi exist in symbiotic
relationships with plant roots to form mycorrhizae or with
algae to form lichens. Some fungi are able to break down or
detoxify wastes and other pollutants (3). A large number of
fungi survive as saprobes recycling nutrients in ecosystems,
such as carbon, nitrogen, and sulfur. Unfortunately, some of
these saprobes have been found to grow in the indoor envi-
ronments of buildings and have led to building related
complaints and illnesses (4–7). Samson (8) estimated that
100–149 species occurs indoors, while Miller and Day (9)
found approximately 270 species recovered from the dust
indoors (10). Li and Yang (11) found that over 600 species
were identified from samples collected from indoor environ-
ments in North America based on the information in a
database of a commercial laboratory. However, the exact
number still remains unknown. Likely it will exceed 600 spe-
cies, as occasionally a new record is discovered from samples
collected from the indoor environment. A majority of indoor
fungi are anamorphic fungi.
Fungi develop and release their spores into the air for dis-
persal (12). Human beings are often exposed to fungi by inha-
lation of airborne fungal spores, hyphal fragments, and fungal
by-products, especially in indoor environments. Certain
fungi have been associated with asthma and respiratory con-
ditions (13–15).
Fungi produce a variety of secondary metabolites, includ-
ing mycotoxins and some fungal volatile organic com-
pounds (VOC’s), also known as microbial VOCs (MVOCs)
(3,16–18). Mycotoxins are harmful to animals and humans
(19–21) and are suggested as a major possible human health
risk factor in buildings with mold problems (22,23). In addi-
tion to mycotoxins, some MVOCs produced by actively grow-
ing fungi as both primary and secondary metabolites are
known irritants or hazardous chemicals (18,24). They may
pose a health risk to building occupants and workers handling
fungal matter (5,6,25–27).
This chapter reviews the existing literature on airborne
fungi with an emphasis on indoor fungal growth and contam-
ination as well as the principal human health effects of expo-
sure to fungi, mycotoxins, and other by-products. It is
important to note that bacteria (including actinomycetes),
mites, insects, and other microbes may also grow in a wet,
damp indoor environment.
A wealth of literature on outdoor airborne fungi can be
found in reviews by Gregory (28), Flannigan et al. (29), Lacey
(30,31), and Levetin (32,33). It is important to note that
outdoor airborne spores are often the source of indoor fungal
spora. Their impact on indoor airborne fungal populations
could be immediate or delayed until they have settled and
colonized an indoor environment. Sampling of airborne
and indoor fungi is not covered in this chapter. For any issues
or questions related to sampling of indoor and airborne
fungi, refer to chapter 3.2.2 in this book and several guides/
books published by AIHA in the past 10 years (34–36).
AIRBORNE FUNGAL POPULATIONS
It must be emphasized that it is to the selective advantage of
fungi to release, disperse, and disseminate their spores and
occasionally hyphal fragments or partial conidiophores in
air from one location to others. They cannot survive and
complete their life cycles by staying afloat in air for an indef-
inite period of time. The dispersal of fungal spores can be
short or long distance (37,38). The majority disperse their
spores over a short distance. Therefore, when discussing fun-
gal contamination, identifying and locating the source of fun-
gal colonization is often of higher importance than assessing
airborne fungi data (39,40). In addition to airborne dispersal,
some fungi rely on running water, insects, and animals for dis-
persal of their spores (41,42).
A large collection of literature on assessing indoor fun-
gal populations has been accumulated. The majority of
the literature was based on air sampling data. These include
hospitals and health care facilities (43–48), residential
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3.2.5-1
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dwellings (49–55), schools (56–58), and office buildings (59,
60). The focus of hospital sampling was often on Aspergillus
species, including A. fumigatus, an opportunistic human
pathogen (43). General fungal populations were identified
in nonhospital sampling.
A comprehensive assessment of fungal contamination in
the indoor environment should include consideration of fac-
tors such as outdoor air, air conditioning, heating and venti-
lation systems, ventilation mode, heating, occupant density,
ventilation rate, moisture (including water damage, high
relative humidity [RH] in the air, and dampness), mainte-
nance, on-site inspection, air sampling, surface and source
sampling, sample analysis, risk analysis, and finally remedial
actions (49,61). Unfortunately, the majority of investigations
fail to follow the approach of comprehensive assessment,
often due to insufficient strategy, labor, time, and funds as well
as understanding of environments and ecosystems indoors.
An alternate approach to identifying indoor fungal contami-
nation is to focus on inspection and surface/source sampling.
Factors Affecting Airborne Fungal Populations
Three important factors that directly affect airborne fungal
populations are the availability of food/substrates and free
water for fungal growth and the methods of spore dispersal.
Other physical, chemical, and biological parameters affecting
fungal growth, and subsequent airborne fungal populations,
can be found in recent references (2,3,8,41).
Substrates (Including Water Activity)
Fungi are achlorophyllous and heterotrophic, take up
nutrients by absorption from substrates, and require simple
sugars, carbohydrates, and other organics, such as vitamins,
amino acids, and essential mineral elements to survive (3).
In the natural environment, fungi have developed a number
of ways to obtain these nutrients (3), such as necrotrophic,
symbiotic, and saprotrophic relationships.
Humans share food, living space, environments, and
resources with fungi. We utilize fungi to produce bread; man-
tou (steamed bun); cheese; edible mushrooms; alcoholic bev-
erages; and useful by-products, such as antibiotics, enzymes,
and organic acids (60). Some fungi cause food spoilage or
make food toxic to humans. Botrytis cinerea is a well-known
pathogenic fungus causing gray mold disease on grapevines,
strawberries, and many other fruits and produce. Species of
Penicillium and Aspergillus often cause spoilage in foodstuffs
and make them inconsumable to animals and humans. On
the other hand, Penicillium camemberti and P. roqueforti are
used in cheese production. Fungi are also known to cause
wood stains, wood decay, biodeterioration, and biodegrada-
tion of polymers, carpet, plaster, drywalls, wallpaper, paints
and organic coatings, fuels and lubricants, leather, fabric
products, paper, and wood products (4,62–65). These refer-
ences underscore the very likelihood that fungi can and will
grow in artificial environments. Consequently, controlling
nutrient sources to limit fungal proliferation/growth is practi-
cally impossible.
One of the critical factors affecting indoor fungal growth is
water. There are a number of ways to measure water availabil-
ity in materials. Water or moisture content of a material is
expressed as a percentage of the oven dry weight (65). How-
ever, water content does not suggest the actual availability of
free water in the material to fungi. A better measurement of
water availability to fungi is water activity. Water activity is
numerically equal to equilibrium relative humidity (ERH)
expressed as a decimal. If a sample of substrate is held at
constant temperature in a sealed enclosure until the water
in the sample reaches equilibrium with the water vapor in
the enclosure, then a
w
= ERH/100. Another expression is:
aw¼vapor pressure of water in substrate
vapor pressure of pure water
A detailed discussion of water activity of fungi in food and
materials is presented by Gravesen et al. (4), Hocking and
Miscamble (66), Li and Yang (40), Smith and Onion (67),
Troller and Scott (68), Adan et al. (69), and Huinink and
Adan (70).
Many common indoor fungi are hydrophilic and require
a
w
near 1 for growth. Some xerophilic fungi, however, have
optimal water activity ranging from 0.65 to 0.90 (4). Both
mesophilic and xerophilic fungi can be found in the indoor
environment. Table 1 lists some hydrophilic, mesophilic,
and xerophilic fungi and their minimum a
w
. It should be
noted that a very short period of peak humidity, even below
saturation RH, may lead to fungal growth. Adan et al. (69)
showed that it took only 69 h for Penicillium chrysogenum
Thom to develop from spore germination to sporulation
and 73 h to develop mycelial mass on pure gypsum at 21°C
and 97% RH observed with cryo-SEM.
Fungal Spore Discharge Mechanisms
Fungal spores are released by two basic mechanisms: (1)
active spore discharge and (2) passive spore release. Concen-
trations of certain airborne fungal spores have been known to
peak during certain hours of the day or night. This periodicity
is related to spore discharge mechanisms and environmental
factors in nature (28,30,42). Details of these two mecha-
nisms and environmental factors affecting spore release are
presented by Lacey (30) and Levetin (33).
Fungi with active spore discharge include such common
airborne fungi as Sporobolomyces,Epicoccum,Nigrospora, and
some smut-like yeasts. Many ascospores and basidiospores
also have active discharge mechanisms (33). Sporobolomyces
and some basidiospores are usually most abundant at night
or in the predawn hours. Their spore release requires the
absorption of moisture to build-up release pressure or forming
a droplet at the hilar area. Dry spore fungi, such as Aspergillus,
Penicillium,andCladosporium, are often hydrophobic. They
become airborne by passive force, such as air movement or
rain droplets (71,72). Cladosporium usually dominates the air-
borne spore population during the day. Its spores stay airborne
owing to the buoyancy of warmer air.
Some fungi, such as puffballs (Calvatia,Lycoperdon,Sclero-
derma) of basidiomycetes, are able to produce a huge number
of spores and release their spores in “spore clouds or puffs”
when affected by raindrops, humans, or small animals (33,
71–73). The spore clouds may persist for a period of time until
air mixing and dilution disperse them. Results of air sampling
can be greatly affected by whether the spore cloud has dis-
persed (31).
Many fungi that are frequently detected indoors and out-
doors produce spores in a slimy mass. These include such
common indoor contaminants as Acremonium (although
some species of Acremonium produce dry spores), Aureobasi-
dium,Fusarium,Phoma,Stachybotrys,Trichoderma, and yeasts.
Slimy spores may be released into the air when they become
dry, disturbed, or attached to other particles. Their dissemina-
tion is often assisted by insects, mites, small animals, or water
(42). Because slimy spores do not become airborne easily,
their detection indoors should be considered significant.
Any detection of Stachybotrys in air samples taken indoors
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should trigger further investigation and search for the con-
firmed presence of this fungus.
Airborne Fungal Populations
Fungi as a group produce a number of different spores, both
sexual and asexual. Many types of spores are capable of
becoming airborne. Some spores, such as chlamydospores
(asexual) and zygospores (sexual), are not designed to be dis-
persed by air transmission, and there has been no report of
recovering these spores in air or they are rarely observed in
the air, such as spores of Glomus species (Klironomos, unpub-
lished data). Hypogeous fungi (including such well-known
fungi as truffles) produce subterranean sporocarps and dis-
perse their spores through different mechanisms. However,
both sexual and asexual spores of four major groups (Myxo-
mycetes, zygomycetous fungi, Ascomycetes including ana-
morphic fungi [ formerly classified as Deuteromycetes], and
Basidiomcetes) have been isolated and reported from air.
Spores of Ascomycetes and Basidiomycetes have fre-
quently been recovered from air samples using spore trap sam-
plers. Levetin (41) reported 18 genera of basidiospores from
the atmosphere in Tulsa, Oklahoma. Furthermore, many spe-
cies of basidiospores have been demonstrated to be allergenic
(74–80). The importance of basidiomycetes in the indoor
environment depends on the building construction. Wood-
inhabiting basidiomycetes, such as polypores, are associated
with wood decay and may be found in buildings constructed
of wood. In fact, wood decay caused by polypores is a signifi-
cant problem in the United Kingdom (81) and in the United
States (65). A number of Coprinus species and several other
mushrooms were found growing in buildings with water dam-
age (82). Unfortunately, identification of airborne basidio-
mycetes collected using culture techniques can be difficult
and they are often missed or misidentified. A real-time
PCR test has been developed for the detection of dry-rot
fungi, Meruliporia incrassata and Serpula lacrymans (83).
Ascospores have been identified from air samples using
spore traps (84). Many Ascomycetes, however, do not pro-
duce ascomata and ascospores in culture. This makes it diffi-
cult to determine the frequency of occurrence of ascospores in
air. Some ascomycetes, such as Ascotricha,Chaetomium,
Emericella, and Eurotium (both Emericella and Eurotium are
teleomorphs of some Aspergillus species) are commonly
formed in cultures. Ascomata of species of Ascotricha,Peziza,
and Pyronema are frequently observed or reported from indoor
environments (11,85). This demonstrates that ascospores
may become airborne. Ascospores are suspected to be aller-
genic. Four species of Chaetomium were listed as licensed
by the FDA for commercial production as allergens (84).
Rivera-Mariani et al. (86) demonstrated that out of 33 aller-
gic rhinitis and asthmatic patients in Puerto Rico, 31 reacted
to ascospores, 29 to basidiospores, 19 to hyphae/fungal frag-
ments, and 12 to mitospores. They stated that sensitization
to airborne spores of basidiomycetes, ascomycetes, and fungal
fragments seem to be more prevalent than to similar numbers
of conidia in patients with active allergies, suggesting a possi-
ble role in exacerbations of respiratory allergies in tropical
environments. Otherwise, little documentation is available
on the allergenicity of ascospores.
The majority of airborne fungi collected on samplers and
grown on agar media are anamorphic fungi and zygomycetous
fungi. Most anamorphic fungi are asexual states of Ascomy-
cota and a minority Basidiomycota. Asexual spores of ana-
morphic fungi are called conidia, and of zygomycetous
fungi, sporangiospores. Many of these spores are known aller-
gens. Some of them have been prepared into allergen extracts
TABLE 1 Selected fungi and their a
wb
a
w
T (°C) a
w
T (°C)
Absidia corymbifera 0.88 25 Paecilomyces variotii 0.84 25
Alternaria citri 0.84 25 Penicillium brevicompactum 0.81 23
Aspergillus candidus 0.75 25 P. chrysogenum 0.79 25
A. flavus 0.78 33 P. citrinum 0.80 25
A. fumigatus 0.82 25 P. corylophilum 0.80 25
A. niger 0.77 35 P. expansum 0.83 23
A. ochraceus 0.77 25 P. frequentans 0.81 23
A. restrictus 0.75 25 P. griseofulvum 0.81 23
A. sydowii 0.78 25 P. spinulosum 0.80 25
A. terreus 0.78 37 Phoma herbarum 0.93 25
A. versicolor 0.78 37 Rhizopus microsporus 0.90 25
A. wentii 0.84 25 R. stolonifer 0.84 25
Cladosporium cladosporioides 0.84 25 R. oryzae 0.88 25
Cladosporium sphaerospermum 0.84 25 Scopulariopsis brevicaulis 0.90 NA
Eurotium
a
amstelodami 0.70 25 Sistotrema brinkmannii 0.97 25
Eurotium chevalieri 0.71 33 Stachybotrys chartarum 0.93 25
Emericella
a
nidulans 0.78 37 Syncephalastrum racemosum 0.84 25
Fusarium moniliforme 0.89 25 Trichoderma harzianum 0.91 25
Geomyces pannorum 0.89 25 Wallemia sebi 0.70 25
Mucor circinelloides 0.90 25 Ulocladium chartarum 0.89 25
M. plumbeus 0.93 25 U. consortiale 0.89 25
a
Both genera are teleomorphs of Aspergillus.
b
NA, not available. Sources: 40, 65–67; For calculation of a
w
, see text.
3.2.5. Airborne Fungi and Mycotoxins ▪3.2.5-3
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and approved by the FDA for medical uses (84). Common
anamorphic fungi found in air include Alternaria,Aspergillus,
Cladosporium,Epicoccum, and Penicillium.Mucor,Rhizopus,
and Syncephalastrum, all zygomycetous fungi, are also fre-
quently isolated from air.
Another group capable of producing and releasing spores
into the air is the Myxogastria (formerly Myxomycota) or
the true slime molds. Slime molds, as a group, are polyphy-
letic. They are considered to have similarities to both true
fungi and animals (1) and have been placed in the Kingdom
Protista (33,87). Spores of slime molds have been docu-
mented from air samples (28,87). Occasionally, species of
Stemonitis have been found growing in environments such
as a cellar, basement, and window sill underneath a leaking
window air conditioning unit in buildings with water issues
( personal observation). Allergic reactions to extracts of slime
molds have been reported. Giannini et al. (77) reported that
15.4% of patients tested showed positive skin reactions to
extracts of Fuligo septica,Lycogala epidendrum, and Stemonitis
ferruginea. Benaim-Pinto (74) and Santilli et al. (79) found
that patients yielded positive skin responses to spore extracts
of Fuligo septica.
Outdoor airborne fungal populations may directly or indi-
rectly affect the indoor populations as the pathways of infiltra-
tion are often suspected to be from leaks and cracks or through
doors, windows, and air intake systems. Therefore, it is not
surprising that common outdoor fungal taxa are often the
predominant fungal types detected indoors (42,42,88). In
a review of the literature, some agreements and disagreements
exist on the predominant fungi identified indoors. Yang et al.
(88), based on the culture of over 2,000 Andersen samples
collected outdoors and in nonresidential buildings in the
United States, found that Cladosporium,Penicillium,Aspergil-
lus, Basidiomycetes, and Alternaria were the top five fungal
taxa found indoors as well as outdoors in frequency of occur-
rence. All five fungal taxa were detected in less than 40% of
indoor samples. However, Cladosporium was found in over
80% of outdoor samples, and Penicillium was detected in
58%. These suggest that both Cladosporium and Penicillium
are common in outdoor air. The results were somewhat in
agreement with those reported by Strachan et al. (52)from
British homes and by Womble et al. (89) in 86 office build-
ings in the continental United States. Strachan et al. (52)
found that Penicillium,Cladosporium, and Basidiomycetes
(including Sistotrema brinkmanii) were the common types of
mold isolated as well as the predominant mold concentrations
measured. Womble et al. (90) found, in rank order, nonspor-
ulating fungi, Cladosporium,Penicillium, yeast, and Aspergillus
were the most common fungi indoors. Using a number of
different types of samplers and sampling media, VerHoeff
et al. (53) found that species of Cladosporium,Penicillium,
and Aspergillus (including teleomorph Eurotium) were com-
mon in homes in the Netherlands. In a survey of 10 elemen-
tary schools in southern California using an Andersen
sampler, Dungy et al. (56) found that Cladosporium,Alterna-
ria,Penicillium, sterile mycelia, and Epicoccum were the top
five fungal groups isolated indoors. The predominant fungi
detected outdoors were slightly different in that Aureobasi-
dium was more frequently encountered than Epicoccum.How-
ever, using a Roto Rod sampler, they found that spores of
Alternaria, rust fungi, Cladosporium,Epicoccum, and smut
fungi were predominant both indoors and outdoors. Through
further comparison of airborne fungal populations in the same
study, the authors found that the top seven fungal types were
identical at schools and at homes. In a hospital sampl-
ing, Solomon et al. (45) found Aspergillus fumigatus,A. niger,
Mucor,Paecilomyces, and yeasts were the five most common
fungi recovered in culture at 37°C. The agreements and dis-
agreements in the findings may be attributed to differences
in sampling techniques, isolation media used, incubation
temperatures, and geographical areas (42,88).
Shelton et al. (91) evaluated 12,026 fungal air samples
(9,619 indoor samples and 2,407 outdoor samples), collected
from 1,717 buildings located across the United States using
Andersen N6 single-stage samplers. Ninety-nine percent of
the samples were collected with rose bengal agar and the
other 1% with malt extract agar. The culturable airborne fun-
gal concentrations in indoor air werelower than those in out-
door air. However, Stachybotrys chartarum was identified in
the air in 6% of the buildings studied and 1% of the outdoor
samples. The fungal levels were highest in the fall and summer
and lowest in the winterand sprin g.Geographically, the high-
est fungal levels were found in the southwest, far west, and
southeast. Because different fungal isolation media are known
to have different selective effects, the combined use of the
data derived from two different media is inappropriate. The
reliability of fungal identification, data, and sampling quality
control of such a large project must be scrutinized before the
results and conclusions are fully accepted.
In a study of 50 single-family detached homes built since
1945 with less than 0.18 m
2
(or 2 ft
2
) of known water damage,
and located within a central city census tract in the metropol-
itan Atlanta city (DeKalb and Fulton Counties) of Georgia,
air and dust samples were collected for assessment to establish
a baseline of “normal and typical”types and concentrations of
fungi in urban homes (92). The homes were predetermined
not to have noteworthy moisture problems or indoor fungal
growth. The homes were sampled twice (summerand winter)
within a calendar year. Air samples were collected with a Spi-
ral Air System at 180 lpm onto MEA plates. Positive-hole cor-
rection was applied. Dust samples were sieved and inoculated
by the “direct plating”method onto MEA and DG18 media.
Cladosporium cladosporioides,Cladosporium sphaerospermum,
and Cladosporium spp. were the top three fungal species and
group in both indoor and outdoor air samples. The findings
included that rankings by prevalence and abundance of the
types of airborne and dustborne fungal spores did not differ
from winter to summer, nor did the rankings differ when air
samples taken indoors were compared with those taken out-
doors. Water indicator fungi (such as Chaetomium,Stachybo-
trys, and Ulocladium) were essentially absent from both air and
dust samples.
Indoor Sources of Fungi
The detection of airborne fungi does not necessarily suggest
growth and reproduction of fungi indoors. However, it is
believed that actively growing fungi in the indoor environ-
ment are the primary cause of adverse health effects due to
exposure to indoor fungal allergens, mycotoxins, and fungal
MVOCs. It is therefore important to identify and detect infes-
tation sites of fungi indoors. Due to the limitation of correct
identification of fungi, some of the health effects of indoor
fungi are arguably considered not necessarily species-specific,
nevertheless, correct identification of fungi may be important
for practical and research issues.
Many common indoor fungi are strong biodeteriorating
agents and have been reported from various building materi-
als and systems. Raper and Fennell in their classic publication
(93) reported various Aspergilli from building materials, such
as wallpaper and paper products, textiles, jute, insulation
materials, and fabrics. Two species of Aspergillus were isolated
from and found to grow on glass (94). Many species of the
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genus Penicillium, commonly detected in indoor air sampling,
were frequently referred to as food spoilage and biodeteriorat-
ing agents (4,64,85,93). Penicillium chrysogenum is reported
to be the most common fungus indoors (95). However, Scott
et al. (95) found that P. chrysogenum is rare in outdoor air.
P. chrysogenum was further studied by Houbraken et al. (96)
using partial β-tubulin, calmodulin, and RPB2 data sets. Hou-
braken et al. (96) found that Fleming’s penicillin-producing
strain is not Penicillium chrysogenum but P. rubens. It is, there-
fore, P. rubens that is one of most common fungi in indoor
environments, not P. chrysogenum s. str. Gravensen et al.
(4) included a list of 13 fungal species as important molds
in damp buildings. Samson et al. (7,74) described some com-
mon fungal species from indoor environments.
Morgan-Jones and Jacobsen (63) studied moldy carpets,
plasterboard, and wallpaper from three hotels in Florida and
Georgia. Their brief literature review suggested that many
fungi had been reported to cause biodeterioration of paper,
textiles, and plaster. The genera of fungi most often identified
were the ascomycete genus Chaetomium; dematiaceous
hyphomycete genera Alternaria,Cladosporium,Stachybotrys,
and Ulocladium; the moniliaceous hyphomycete genera Acre-
monium,Aspergillus, and Penicillium; and the pycnidial genus
Phoma. In the study, 14 species, including 2 new species of
Cladosporium, in 11 genera were isolated and identified. In a
study of toxicity of moldy building materials, Johanning
et al. (97) not only detected cytotoxicity of the materials to
cell cultures but also identified satratoxin H and spirolac-
tone/lactams and several groups of fungi. The fungi were iso-
lated from gypsum wallboards and other building materials.
The fungi identified included those described by Morgan-
Jones and Jacobsen and additional species of Aspergillus,Pae-
cilomyces, and Trichoderma.
Li and Yang (11) described seven new records or note-
worthy fungi isolated from indoor environments. The
seven species are Ascotricha chartarum,A. erinacea,Memno-
niella echinata,Sporoschisma saccardoi,Stachybotrys microspora,
S. nephrospora, and Zygosporium masonii. All species were
recovered from water-damaged building materials, such as
drywall, wallpaper, or wood. Four species were reported for
the first time from the United States. Li et al. (98) described
a new species from indoor environments in the United States
and Canada. Corda (99) described Stachybotrys chartarum as
S. atra from wallpaper of a residence in Prague in 1837.
In the past several years, mass sequencing techniques
were used to study indoor fungi from dust samples collected
around the world in several studies (100). Amend et al.
(100) found that fungal diversity in the temperate region is
greater than that in the tropical region and building function
does not have significant effect on indoor fungal composi-
tion, despite differences between architecture and materials
of some buildings in close vicinity based on 72 dust samples
collected from six continents. However, Andersen et al.
(101) showed that indoor mycota are associated with differ-
ent building materials: (a) Acremonium spp., Penicillium chrys-
ogenum,Stachybotrys spp., Ulocladium spp. and gypsum and
wallpaper; (b) Arthrinium phaeospermum,Aureobasidium pul-
lulans,Cladosporium herbarum,Trichoderma spp., yeasts and
woods and plywood; and (c) Aspergillus fumigatus,Aspergillus
melleus,Aspergillus niger,Aspergillus ochraceus,Chaetomium
spp., Mucor racemosus,Mucor spinosus, and concrete and
other floor-related materials in Denmark and Greenland.
In addition to building materials, fungi have been known
to grow in the heating, ventilating, and air-condition-
ing system (HVAC) (54,102). Heinemann et al. (103)
studied contamination of fungi, bacteria, and thermophilic
actinomycetes. They sampled surfaces of filters and fans with
RODAC contact plates and water from humidifiers. The
serial dilution method was used for analyzing humidifier
water. A wide variety of fungi were identified. However,
some of the identified fungi were likely spore contaminants
rather than the result of fungal growth. Kemp et al. (104)
studied fungal growth on filters of the HVAC system and
reported isolation of Aspergillus niger,A. fumigatus,Alternaria,
Cladosporium,Mucor sp., Aspergillus sp., and Penicillium sp.
However, they could only confirm growth of Aspergillus sp.,
Cladosporium sp., and Penicillium sp. when filters were directly
examined under the microscope. Buttner et al. (105) reported
a controlled study using three air duct materials (i.e., gal-
vanized metal, rigid fibrous glass ductboard, and fiberglass
duct liner) and Penicillium chrysogenum spores. They found
that fungal growth might occur on a variety of duct materials,
including bare metal, provided soiling and moisture were
present. The results showed that contaminated air ducts
might expose building occupants to high concentrations of
spores dispersed from fungal colonies growing on duct materi-
als during normal operation of the system. Yang (102) exam-
ined and cultured 1,200 fiberglass insulation liner samples
from HVAC systems in the United States and found fungal
colonization and growth in approximately 50% of the samples
studied. Fungal taxa were differentiated based on water and
humidity conditions. Species of Cladosporium and Penicillium
were primarily from areas with high RH, whereas species of
Acremonium,Aureobasidium,Exophiala,Fusarium,Paecilomy-
ces,Phoma,Rhodotorula,Sporobolomyces, and yeasts were sus-
pected in areas subjected to frequent wetting. Cladosporium
cladosporioides,C. herbarum, and C. sphaerospermum were
the primary species identified.
All fungi found to colonize building materials are saprobic
and biodeteriorating agents. Some fungi, such as species of
Chaetomium,Aspergillus,Stachybotrys, and Trichoderma,are
known to be capable of degrading cellulose fibers. Although
at least 270 fungal species have been reported from indoor
environments in the literature (10), it is very likely that any
saprobic, biodeteriogenic, or cellulolytic fung i can potentially
grow indoors if opportunity arises (4,39).
Although species of anamorphic fungi are commonly
detected in moldy building materials, Ascotricha chartarum,
A. erinacea,Chaetomium species, Peziza spp., and Pyronema
domesticum of the Ascomycetes are occasionally found on
damp materials in buildings (11,39,79). The asexual state
of basidiomycetes, such as species of Cryptococcus,Rhodotor-
ula, and Sporobolomyces, are also common in indoor envi-
ronments (39) and Wallemia sebi was often reported from
buildings with dampness or water damage problems. In addi-
tion, Yang (unpublished data) has seen and identified fruiting
structures of a slime mold, Stemonitis sp., and basidiomata
(fruiting bodies of basidiomycetes) of Coprinus spp., Pleurotus,
and Poria from various building materials, from ceiling tiles to
wood products. Samson et al. (85) reported that Sistotrema
brinkmanii, a wood decay fungus, is commonly isolated from
wet, decaying window and door joinery. Mycelia and hyphae
with clamp connections, indicating basidiomycetes, are fre-
quently detected colonizing water-damaged wood structures.
Not surprisingly, wood-inhabiting basidiomycetes are often
wood decay fungi. The wood decay, dry rot fungus Serpula
lacrymans is the most common indoor basidiomycete in
central Europe, while Meruliporia incrassata pendant to S.
lacrymans also received considerable attention in North
America (106). Specimens of S. lacrymans from California
collected in nature were ascribed to var. shastensis while all
other collections, mainly from buildings in Europe, were
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ascribed to var. lacrymans (107). Meruliporia incrassata
(syn. Poria incrassata) and Serpula lacrymans were detected
in building wood samples collected from the United States
by real-time PCR (83). Approximately 80 species of wood
decay fungi have been found in buildings in northern Ger-
many (82,106). Twenty-nine species or genera of basidiomy-
cetes were identified from 3,434 decay fungi occurrences in
Norwegian houses from 2001 to 2003 (108). One hundred
fifty-two species of wood decay fungi were reported from
wood products in the United States (109). It should be
pointed out that these fungi were not isolated from an indoor
environment. The exact number of wood decay fungi from
indoor environments in the United States remains unknown.
FUNGI AND HUMAN HEALTH
Fungi are known in veterinary and human medicine to be a
source of infections, allergies, and irritant-toxic health reac-
tions primarily with symptoms and disorders of the skin,
mucous membranes, or internal organs. Current knowledge
and key concepts are summarized and discussed below (57,
110,111). Expert reviews of reported health problems associ-
ated with building dampness and biological agents, such as
the Institute of Medicine (IOM) (2004) or the WHO-EU
(2009) and others concluded, based on their reviews mainly
of the English-language literature and epidemiological stud-
ies, that dampness-related fungi are associated with allergies,
respiratory symptoms or diseases, such as asthma, and changes
of the immunological system (112–116). In addition, there
are several clinical studies and case reports of adverse health
reactions that include primarily nonallergic adverse effects
to the lungs (bleeding in infants; allergic alveolitis), neuro-
logical system (headaches and cognitive dysfunction), endo-
crine and reproductive organs (thyroid hormonal changes
and menstrual disorders in women), and rheumatological dis-
orders ( joint pain), and an increased risk of cancer has been
also explored. Some of the fungi (maybe in combination with
bacteria) produce chemicals that are known genotoxins and
carcinogens (117–123). However, these are findings that
are difficult to document and validate in epidemiological or
experimental studies and have therefore been considered
debatable by some. Further evidence needs to be obtained.
Fungi and their by-products, such as (1–3)-ß-D-glucan,
mycotoxins, and MVOCs, have been implicated in adverse
health reactions and diseases (7,124–127). Americans spend
up to 90% of their time indoors, where contaminants often
are at higher levels than they are in the ambient air. It is
not uncommon that exposure duration and concentrations
of atypical fungi (fungi associated with excessive dampness)
are greater indoors than outdoors because of occupant life-
styles, building conditions, and materials that lead to fungal
growth and accumulation. Additionally, exposure to biologi-
cal contaminants of all kinds, but particularly molds and bac-
teria, can be high when buildings have moisture problems or
water damage (128). It is estimated that more than 1one third
of buildings in the United States and Western Europe have
severe moisture problems that result in significant fungal
contamination in indoor environments (129–131). Exposure
to high levels of indoor dampness and mold has been associ-
ated with upper and lower respiratory symptoms, including
nasal and sinus irritation, congestion and inflammation,
sore throats and chest burning sensation, cough, wheeze,
chest tightness, and exertional dyspnea in people, according
to several large epidemiological studies cited by the IOM,
WHO, and others (112,113,116,132,133). Clinical case
studies and research have shown that nonallergic health
reactions are common in individuals with atypical fungal
indoor exposure. Typical health complaints of patients living
in indoor environments with excessive fungal exposure are
listed in Table 2.
The medical conditions and illnesses associated with fun-
gal indoor exposure include a spectrum of infectious, skin and
respiratory disorders, allergy, and irritant/toxic health reac-
tions (112,114,125,134). Most of the reported adverse
health reactions are normally of short duration and reversible
after the exposure has been stopped or controlled. In some
cases, the adverse health consequences can be more serious
or may be irreversible, requiring symptomatic treatment and
careful avoidance of microbial triggers (134). Medical condi-
tions are listed in Table 3 and described later in more detail.
Infections
Infections caused by fungi are called mycoses. They are cate-
gorized as endemic mycoses and opportunistic mycoses.
Opportunistic fungal pathogens have a great public health
importance, especially in persons with HIV, with organ fail-
ure, and or receiving organ transplants (135,136). Endemic
mycoses are related to the geographical distribution of certain
fungal pathogens. These types of infection are caused by the
inhalation of airborne spores or conidia found in certain
regions where there is a higher frequency of such fungi
because of unique soil and plant/flora conditions (30,111,
137). Table 4 lists several important fungi and the infections
that occur through air transmission, the diseases they cause,
and clinical manifestations.
Opportunistic infections are secondary complications that
occur in patients with an altered or weakened immune sys-
tem. Patients at risk for fungal infections usually have major
systemic diseases or health suppressed conditions such as
complicated diabetes mellitus, cancer, HIV/AIDS, severe
liver or kidney diseases, organ transplantation, and burn
injury or may be on immune-suppressive medication treat-
ment. An endemic outbreak of fungal meningitis, spinal
infections, and other serious health complications in 2012
appeared to be caused by injecting directly into the spinal
fluid of patients a steroid medication for pain control, meth-
ylprednisolone acetate, from a compounding pharmacy
that reportedly was contaminated by Exserohilum rostratum,
Aspergillus fumigatus,Stachybotrys chartarum,Cladosporium,
TABLE 2 Complaints and symptoms reported by patients with
exposure to excessive fungal growth
Headaches
Runny nose or nasal congestion
Burning sensation and watery eyes
Sore throat and hoarseness
Sneezing or irritant-dry cough, chest tightness and burning chest
sensation, shortness of breath, wheezing
Unusual nosebleeds and coughing up blood (rare)
Skin and mucous membrane irritation (occasionally hair loss)
Dizziness, concentration and memory problems; cognitive
dysfunction
Severe fatigue and exhaustion (physical and/or mental);
Nausea, (vomiting) and gastrointestinal problems (loose stools,
stomachaches)
Feverish feeling
Joint and muscle ache (flu-like reaction)
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and several other fungi (139). The outbreak was associated
with more than 39 deaths out of 620 cases in multiple states
by mid-December 2012 (140). These iatrogenic fungal
infections were likely the result of contamination during
the medication production process in an unhygienic indoor
environment. These infections are not contagious, and the
fungi are not considered obligatory pathogens. Secondary
fungal infections and medical complications related to air-
borne fungal contamination in hospitals and transplant units
have been reported. Immunocompromised patients may be at
an increased risk for opportunistic infections if pathogenic
fungi become airborne and are significantly elevated in
indoor air surveys. Among the fungi of concern are Aspergillus
spp., such as A. fumigatus,A. flavus, and A. niger. Soil, bird
and bat droppings, water-damaged materials, or organic-rich
substrates in buildings may be a reservoir for these fungi
(39,57,141). Other clinically important fungal infections
are candidiasis with local mucocutaneous or disseminated
systemic organ manifestations and skin mycoses, such as
dermatophytoses, keratomycosis, tinea nigra, piedra, and
malassezia-caused dermatitis. Invasive fungal diseases of the
paranasal sinuses may also be associated with allergic sinusitis
in atopic patients (142). Aspergillus species are often
involved. Noninvasive forms may colonize preexisting body
cavities and may be asymptomatic as long as some immuno-
logical resistance can be maintained. Chronic rhinosinusitis
with eosinophilic inflammation of the airways has been
linked to dampness-related fungi from indoor environments
and may also be related to the development of asthma
(143–145). The beneficial use of antifungals (i.e., itracona-
zole) has been observed in treatment of respiratory conditions
such as chronic sinusitis and asthma, suggesting a combined
effect of infections and inflammation (146–149).
The prevention, diagnosis, and therapy of opportunistic
infections may be difficult for those who are not well trained
and experienced in this field. Early recognition, preventive
building engineering, hygiene, and public health interven-
tion can reduce the incidence of mycosis, especially the insti-
tutional or iatrogenic acquisition in care facilities.
Allergy and Respiratory Diseases
Fungi are known to cause an immune pathology with an exag-
gerated or inappropriate immune response, called hypersensi-
tivity reaction or common allergy (114). The important types
of the allergic immune reactions according to the Coomb-
Gell classification are listed in Table 5, but in the clinical
context these often occur with overlapping presentation.
The fungal spore is a known cause of allergic diseases (150–
152) and was identified as one of the major indoor allergens
(114,153). However, there are still significant methodologi-
cal problems in the production of reliable allergen extract
from fungi compared to cats, dust mites, and other better char-
acterized allergens. Extracts that were available often corre-
sponded poorly with the fungi frequentlyfound in indoor
surveys (154). Many extracts of common indoor fungi are
not available for clinical allergy testing. Several recent epide-
miological studies have shown that long-duration indoor
exposure to certain fungi can result in hypersensitivity reac-
tion and chronic diseases. Mold levels and fungi comparable
to outside background levels and types are usually well toler-
ated by most people. Normal or “typical”indoor molds may
vary depending on climate variations and geographical
TABLE 3 Medical conditions associated with indoor fungal exposure
Organ system Clinical effect Exposure
Upper airways: Nose, sinuses, and
throat
Rhinitis, sinusitis, laryngitis Fungi, allergens, irritants,
MVOCs, particles
Lower airways: lung with bronchial
system and alveoli
Bronchitis, asthma, bronchiolitis, asthma,
allergic bronchopulmonary aspergillosis,
allergic extrinsic alveolitis (a.k.a.
hypersensitivity pneumonitis); toxic
alveolitis and pneumonitis
Fungi, allergens, fungal
by-products. Fine, ultra-fine
particles
Combined upper and lower airway Aspergillosis Fungal rhinosinusitis Fungi, particles
Skin and mucous membrane Urticaria, dermatitis (allergic vs. irritant),
conjunctivitis
Fungal irritants, allergens,
Other organs: central nervous
system, immune system, liver,
kidney, endocrine system
Overlapping diagnoses, differential
diagnoses (exclusion of unrelated
conditions)
Fungi, organic dusts, microbial
by-products
TABLE 4 Diseases transmitted by airborne fungi and affected tissues
a
Fungi Disease Affected organ/tissues
Histoplasma capsulatum Histoplasmosis Lung, eye (skin and bone)
Cryptococcus neoformans Cryptococcosis Lung, central nervous system, meninges, skin, and viscera
Coccidioides immitis Coccidioidomycosis Lung, multi-organ dissemination (skin, bone, meninges, joints)
Blastomyces dermatitidis Blastomycosis Lung, skin and mucous membrane, bone, joints
Aspergillus spp., particularly A. fumigatus Aspergillosis Lung, bronchial airways and sinus cavities, ear canal, eye (cornea)
Sporotrix schenkii Sporotrichosis Granulomatous pneumonitis (rare), skin, joints, central nervous system, eyes
Mucorales, zygomycetes Mucormycosis Nose, sinuses, eye, lung (brain and other organs), gastrointestinal system
a
Sources: 112,138.
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regions. However, when types of mold and levels that are
“atypical”in the indoor environment increase because of
recurrent water leaks, home dampness, and high humidity,
the prevalence of allergy and respiratory problems also rises
(29,39,40,52,155–161). Dampness and mold have, in
many epidemiological studies, been shown to be associated
with cough, environmental lung disease, and asthma (116,
162–166). Molds found on wet building materials and known
to be associated with allergy and respiratory problems are spe-
cies of Alternaria,Aspergillus,Aureobasidium,Cladosporium,
Fusarium,Paecilomyces,Phoma,Penicillium,Rhizopus,Stachy-
botrys,Trichoderma, and others (7,79,97,101,167,168).
The prevalence of allergy to fungi among atopic patients is
estimated to be around 30% and in the general population up
to 6%. Exposure to molds during childhood is suspected to be
a risk factor for development of allergic respiratory disease
(169,170), although a possible protective effect has been
reported concerning children’s microbial exposure in farm
environments (171–173). New onset of asthma in children
after prolonged moisture and mold exposure has been demon-
strated in a prospective study (170). However, respiratory
problems can occur in atopic and nonatopic individuals
(atopy is a genetic trait of increased allergen sensitivity).
The reported percentages of populations allergic to molds
vary from 2% to 18%. Approximately 80% of asthmatics were
reported to be allergic to molds (29). In a 2002 study, up to
35% of newly diagnosed asthma cases were attributable to
workplace mold exposure (172). A recent study in Europe
found that workplace exposure to dampness and molds is
associated with the occurrence of new-onset asthma. In
addition, exposed workers suffering from asthma-like symp-
toms are subject to an increased risk for the development of
asthma (174).
The incidence and prevalence of allergic diseases is on the
rise (114). Many patients with chronic rhinosinusitis have a
very high incidence of positive fungal cultures (up to 96%),
and it is often associated with allergic fungal sinusitis (144).
Park et al. (145) found building-related (BR) rhinosinusitis
symptoms were a risk factor for the onset and development
of BR asthma symptoms and exposure to molds in water dam-
aged buildings is an increased risk for the development of BR
asthma symptoms among the individuals with BR rhino-
sinusitis symptoms. Murr et al. (175) found that Alternaria
alternata,Cladosporium cladosporioides,Cladosporium herba-
rum,Penicillium brevicompactum,Penicillium crustosum, and
Penicillium chrysogenum were at very high concentrations
ranging from 1,451 to 2,867,839 cells equivalence/sample
in the sinus samples of some chronic rhinosinusitis (CRS)
patients. However, the Environmental Relative Moldiness
Index (ERMI) results did not show significant difference in
fungi in the dust samples between homes of CRS and
non-CRS patients.
ERMI is a DNA-based method, based on a collection
of approximately 1,000 dust samples collected from U.S.
houses, developed to screen indoor environments for molds
(176). This method provided alternative tools to the
morphology-based methods for indoor mold research and
investigation. However, ERMI is still subject to debate and
further evaluation and validation. It is questionable whether
ERMI should be applied to nonresidential environments. It
has not been widely accepted as a valid exposure marker at
present.
In clinical allergy studies, patients can be tested for specific
mold allergy using skin or serological tests (IgE-RAST), and
appropriate advice and treatment can then be prescribed. Due
to the low sensitivity of some of the commercially available
mold extract tests, false negative results are not uncommon.
Patients with an atopy are frequently allergic to multiple fun-
gal species and manifest type I reactions (Table 5). Another
practical problem is that available mold extracts at present
only cover a very small portion of molds we are exposed to
and that are common in buildings with dampness and water
damage.
Most of the fungi in bioaerosols may be allergenic depend-
ing on the exposure situation and doses (114), although the
sensitivity of clinical tests may vary with the study population
and individual immune system characteristics. Atopic indi-
viduals typically have a higher rate of positive skin reactions
after provocation tests and serological allergy tests measuring
antibody precipitins (IgE). Diseases such as allergic broncho-
pulmonary aspergillosis (138) and allergic fungal sinusitis
possibly require additional host factors which are not well
documented (144), and may be the result of a combined reac-
tion of allergenic inflammation and the immunotoxic effect
of fungal metabolites. The relevant route of exposure is inha-
lation. Fungal by-products (i.e., mycotoxins) have ciliostatic
effects in the respiratory tract (177), which can be one of the
important pathological mechanisms causing diminished
mucociliary clearing and local inflammatory effects in the air-
ways and sinuses. In general, the adverse effects of fungal
inhalation are related to duration and intensity of fungal
exposure. However, typical for allergic reactions is that once
an individual develops an allergy to certain fungi, even small
airborne concentrations can trigger an asthma attack or other
allergic reactions. This is principally different from fungal
toxic-inflammatory health reactions, which depend on air-
borne concentrations and will be similar for most people,
whether or not they are sensitized. Allergy “threshold levels”
to common mold have been reported (151), but variations in
sampling strategies and methodological limitations make
these very unreliable in practical settings (178,179). There-
fore, the consensus is that acceptable safe threshold limits for
fungal indoor exposure cannot be established (17,180), and it
is generally recommended to avoid or minimize unnecessary
indoor fungal exposures (181).
Although a low rate of IgE-mediated allergic responses to
the toxigenic fungi Stachybotrys chartarum have been reported
in some studies, it is unlikely a strong allergen in the clini-
cal setting, and the toxic-irritant effects appear to be more
important (182). Chun et al. (183) established a suggested
TABLE 5 Immunopathological responses caused by fungal hypersensitivity
Type Immune response Diseases
I: immediate hypersensitivity IgE, mast cell Asthma, rhinitis, eczema, and hay fever
III: immune complex
mediated
IgG, antigen/antibody complexes deposition
in the blood vessels and tissues
Hypersensitivity pneumonitis, Arthus
reaction, extrinsic allergic alveolitis
IV: delayed-type
hypersensitivity
Antigen-sensitized T-lymphocyte Allergic contact dermatitis, pneumonitis
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threshold dose (10 μg) for S. chartarum allergy induction by
comparing the allergenicity of S. chartarum to house dust
mite extracts in a mouse model. They opined that exposure
to S. chartarum might be easily over the sensitization thresh-
old for a susceptible population in buildings with damp or
water-damaged conditions.
Nagayoshi et al. (184) reported for the first time that
inhalation exposure to the conidia of S. chartarum resulted
in the remodeling of pulmonary arteries and pulmonary
hypertension in mice. Yike and Dearborn (185) considered
it a significant step to understand the pathologic effects of
S. chartarum. Rakkestad et al. (186) demonstrated that heat-
treated S. chartarum conidia induced cell death (apoptosis)
within 3–6 h due to DNA damage.
Hypersensitivity Pneumonitis and Organic
Dust Toxic Syndrome
The clinical features, biochemistry, and pathophysiology of
allergic or inflammatory-toxic reactions to airborne microbial
exposure are difficult to separate (187,188). Hypersensitivity
pneumonitis (HP), also called extrinsic allergic alveolitis, is a
well-recognized occupational disease. Table 6 lists several
fungi, their sources, and the occupational hypersensitivity
diseases they cause. Organic dust toxic syndrome (ODTS),
also called toxic pneumonitis, is a nonallergic, noninfectious
form of an acute inflammatory lung reaction to high fungal
dust exposure (89,189,190). The differences between HP
and ODTS can be difficult to distinguish. Table 7 lists com-
parative features of HP and ODTS. The significance of
ODTS in occupational health is such that preventive meas-
ures have been recommended for certain occupations
(agriculture) by the National Institute for Occupational
Safety and Health. The measures include the use of industrial
hygiene controls, special protective equipment, ventilation,
and respiratory protection (192). Although ODTS is more
likely to occur in settings where large amounts of organic
waste are handled (such as agriculture and composting
facilities), it may also happen in office and domestic environ-
ments (189).
Large-scale composting of organic waste is a new, growing
technology in municipal waste management (191). Environ-
mental monitoring suggests that this procedure involves risks
of high levels of exposure to several pathogenic fungi and
bacteria. Immunological blood changes (such as IgG anti-
body elevation) can be observed in waste-handling workers
or other occupations with high fungal exposure (193).
Cladosporium cladosporioides,Cladosporium sp., and Fusa-
rium napiforme were reported to cause HP in residences
(194–196). HP caused by fungi was recently reviewed by Sel-
man et al. (197). Bhan et al. (198) indicated that Stachybotrys
chartarum is a potential cause of HP which is TLR9-depend-
ent in mouse model.
Mycotoxins and Human Health
Fungi produce toxic chemicals, such as the poisonous
compounds found in some mushrooms and the toxic metab-
olites of some species of microfungi. Many of the mushroom
poisons are polypeptides or amino acid–derived toxins (42).
Poisoning due to ingestion of poisonous mushrooms is
excluded from the scope of this chapter, and the reader
should consult suggested references on mushroom toxins
(199,200).
TABLE 6 Fungal agents of HP and occupational dust exposure
Fungal agent Sources Disease
Aspergillus clavatus Moldy malt Malt worker’s lung
Aureobasidium pullulans Steam Sauna-taker’s lung
Alternaria spp. Wood Wood worker’s lung
Botrytis cincerea Moldy fruits Winegrowers’lung
Cryptostroma corticale Wood Maple bark stripper’s lung
Farnai rectivirgula Straw Potato riddler’s lung
Serpula (Merulius)lacrymans Moldy building Dry rot lung
Penicillium spp. Cork Suberosis, woodman’s disease
Penicillium casei Cheese Cheese worker’s lung
Mucor stolonifer Moldy paprika Paprika worker’s lung
Trichosporon cutaneum House dust Japan summer pneumonitis
TABLE 7 Comparative features of HP and ODTS
a
HP (extrinsic allergic alveolitis) OTDS (toxic pneumonitis)
Immune responses Type IV delayed hypersensitivity, cell-mediated
immune reaction
Nonallergenic, noninfectious, lack of IgG.
Affected tissue/organ Lung alveoli, forming granulomas Inflammatory lung reaction
Exposure levels 10
6
–10
10
CFU/m
3
of thermophilic actinomycetes or
fungi
High concentrations of fungi, >10
9
spores/m
3
,
>1–2 µg/m
3
of endotoxins, or (1–3)-ß-D-glucan.
Clinical features Dypnea, cough, fatigue, poor appetite, weight loss,
abnormal chest X ray, abnormal pulmonary
functions, high antibody precipitins; may cause
pulmonary fibrosis long term
Dypnea, cough, headaches, fever, chills, malaise,
acute inflammatory lung reaction, negative chest X
ray; may recover after exposure cessation
a
Source: 191.
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Some fungi have been known to produce secondary
metabolites called mycotoxins that are harmful to animals
and humans (19–21), and specifically when ingested (201,
202), inhaled (5,156,203,204), or in contact with the
skin (205–207). Mycotoxins in food and feed may lead to
cancer and mutagenicity, and estrogenic, gastrointestinal,
and kidney disorders. Some mycotoxins are immunosuppres-
sive and compromise the resistance to infectious disease. In
food safety mycotoxins are well recognized and regulated as
potential disease agents affecting human and animal health
(see “scientific opinion”at http://www.efsa.europa.eu/en/
topics/topic/mycotoxins.htm).
A recent study found that settled dust collected from
moisture-damaged, damp schools contained larger numbers
of microbial secondary metabolites at higher levels than the
dust samples from schools without moisture damage and
dampness (208). Mycotoxin production is species specific
(22,209). Nielsen and Frisvad (22) pointed out the six chal-
lenges faced in mycotoxin research at present. Among the
challenges, flaws in methodology and misidentification of
mycotoxigenic fungi or using sequences generated from mis-
identified cultures had led to some questionable results,
such as false negative or positive results. The most important
one among these hurdles is expertise.
These mycotoxins belong chemically to the alkaloids,
cyclopeptides, and coumarins (3). Early reports of the delete-
rious and poisonous effects of mycotoxins on human health
goes back to the 1100s on ergotism (holy fire or St. Anthony’s
fire) caused by consumption of rye bread contaminated by the
alkaloid-containing ergot developed by Claviceps purpurea
(210). At present, more than 400 mycotoxins have been dis-
covered (207). The total number of mycotoxins remains
unknown but is believed to be in the thousands.
The effects of toxins produced by molds in humans have
been mostly described and researched in relationship to food-
borne diseases affecting animals or regional human disease
outbreaks (202,211). The earliest known mycotoxin pro-
ducers, primarily Claviceps purpurea, produce the substance
ergot, which causes ergotism. Ergot toxins caused food poi-
soning outbreaks due to the consumption of contaminated
rye bread. The toxin was associated with bizarre behaviors
(known as “dancing plague,”“holy fire,”or “St. Vitus’s
dance”) and may have contributed to the population decline
in Europe from the fourteenth to the eighteenth centuries
(210,212).
There has been a debate regarding the public health
importance of “toxic mold”in enclosed indoor environments
and its impact on the occupants’health (213,214). Aspergil-
lus versicolor and species of Penicillium,Fusarium,Trichoderma,
Cephalosporium,Chaetomium, and Stachybotrys are known to
produce naturally potent mycotoxins, depending on available
nutrients, favorable environmental conditions, or their life
cycle. Health complaints and clinical findings in patients liv-
ing or working in wet and moldy buildings often cannot be
explained as allergic reactions in otherwise healthy individu-
als. An overview of clinically important health disorders
based on various case reports and results of disease cluster
investigations are presented for the most important myco-
toxin producers (Table 8)(215–217).
The toxicological knowledge of such mycotoxins pri-
marily stems from the veterinary and food-safety science
(218). A limited number of the more than 400 known myco-
toxins have been studied and found to have important geno-
toxic, mutagenic, cytotoxic, carcinogenic, nephrotoxic,
pseudo-estrogenic, immunosuppressive, protein synthesis
inhibitor, or other toxic properties (19–21,219,220). The
knowledge of these adverse health effects has led internation-
ally to regulatory efforts to protect humans from excess expo-
sure in food and agricultural products based in many cases on
a“precautionary principle,”in part because the data are still
limited and definite dose-response models have not yet
been established for these agents. Toxic molds can induce
abortions and reproductive abnormalities in animals. There
is a concern among environmental health clinicians about
similar effects in humans, however adequate human studies
are lacking. The International Agency for Research on Can-
cer (IARC) classified aflatoxin produced by Aspergillus flavus,
A. niger, and A. parasiticus as having “sufficient evidence”for
human and animal liver carcinogenicity (217). Ochratoxin A
is a potent nephrotoxin with immunosuppressive, terato-
genic, and carcinogenic properties and has been classified
as a possible carcinogen to humans (85,221). Sterigmatocys-
tin is also a carcinogen (224). Whether patulin is carcino-
genic is subject to further research. A recent study showed
the possible role of free radicals in patulin-mediated dermal
tumorigenicity involving mitogen-activated protein kinase
(222). Fumonisins (B1 and B2) are cancer-promoting metab-
olites (223,224). Many of the other mycotoxins have not
been classified as carcinogens, but carcinogenicity cannot
be ruled out due to a lack of appropriate studies.
Human cases of true mycotoxicosis appear to be rare and
in the past were thought to be mostly related to ingestion of
contaminated grain products. However, possible occupa-
tional or environmental inhalation exposures have been
described in recent case studies and epidemiological surveys.
Typical nonallergic symptoms of patients in which myco-
toxin exposure was either confirmed or highly suspected are
recurrent cold and flu–like symptoms, extreme fatigue, con-
stant sore throat or skin irritation, severe and unusual head-
aches, neuromuscular and neurocognitive dysfunction
(tremor and shakes, unusual memory and concentration prob-
lems), bleeding disorders of the lung in infants, irregular
menses, diarrhea, dermatitis and irritation of skin, and
impaired immune function (23,225–229). Mycotoxins may
also be involved in occupational diseases and respiratory can-
cers among food and grain workers (230–232). Environmen-
tal sentinel investigations in water-damaged buildings have
shown detectable levels of airborne mycotoxins from Stachy-
botrys chartarum and others that may be of concern (233–
236). This is important in clean-up and remediation projects,
as the removal of toxins from water-damaged and moldy
building materials is difficult (237). Further studies are
needed to improve our understanding of mycotoxins found
in the indoor environment and possible adverse human
health effects.
Some mycotoxins, such as lysergic acid, are derivatives of
amino acids (such as tryptophan). Others derived from other
precursors are grouped into aromatic and phenolic–related
toxins and terpenoid toxins. Some well-known and potent
mycotoxins in the aromatic and phenolic–related toxin group
are aflatoxin, zearalenone, and griseofulvin. The terpenoid
toxins include trichothecenes and fusidanes (3). There
were more than 200 mycotoxins produced bya variety of com-
mon fungi according to the WHO Environmental Health
Criteria 105 on mycotoxins, published in 1990 (238). Sam-
son (127) suggested that there were more than 400 toxic
metabolites in 1992. It is likely that the number of recorded
toxic metabolites will increase over time because of new dis-
coveries (216,239,240). These alcohol- and water-soluble
toxins can be attached to spores, mycelia, or dust particles
and are sufficiently small in size (2–10 micron) to be inhaled
into the human lungs. Some mycotoxins are lipid soluble and
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may be absorbed via skin. Building materials contaminated
with the above-mentioned fungi have been shown to produce
detectable levels of mycotoxins on the materials (97,167,
168,241).
Aflatoxin may be involved in occupational respiratory
cancers among food and grain workers (242). Aflatoxin-
induced disease has been well reviewed (217,243,244). Tri-
chothecene toxins (T-2 toxin, Fusarium toxins) are listed
with “limited evidence”for animals and “inadequate evi-
dence”(no data available) for humans (217). Macrocyclic
trichothecenes, such as satratoxin H, have not been classified.
Epidemiological studies suggest a higher rate of upper respira-
tory tract and lung cancer in workers in the grain and food-
handling industry with high fungal product inhalation risk
(230). The high rate of lung cancer among uranium miners
in Slesien (Schneeberg disease), may be related to combined
effects of high radon and Aspergillus exposure in the under-
ground mines (244).
Research has shown that water-damaged building materi-
als are often contaminated with fungi that produce detectable
levels of mycotoxins (157,167,245,246), which may
become airborne and further contribute to indoor air pollu-
tion (101,241). From a public health point of view, probable
important toxigenic fungi are Aspergillus species, Penicillium
species, Fusarium species, S. chartarum (syn. S. atra), Paecilo-
myces species, and Trichoderma species. These fungi have
been associated with adverse health effects in humans and
animals resulting in typical organ damage and disease, which
is often neither allergic nor infectious in nature. In several dis-
ease outbreaks, human and animal death has been linked to
exposure to toxigenic fungi, typically through ingestion. Cur-
rent research, however, indicates that inhalation of certain
mycotoxins has even stronger effects (247) and may be fre-
quently associated with health complaints and human dis-
ease. The occurrence of mycotoxins in the environment,
their chemistry and related adverse health effects have been
reviewed (5,20,21,127,206,216,248). Several mycotoxins,
even in low concentrations, were observed to be cytotoxic,
interfere with DNA and RNA synthesis, inhibit protein syn-
thesis, and cause apoptosis of cells of different body organs.
These toxic effects may cause a variety of short-term as well
as long-term adverse health effects in animals and humans
(21,168,248–250). Samson (127) divided the effects into
four basic categories: acute, chronic, mutagenic, and terato-
genic. Symptoms thought to be due to mycotoxins or toxin-
containing spores ( particularly those of S. chartarum) include
dermatitis, recurring cold and flu–like symptoms, burning
sore throat, headaches and excessive fatigue, diarrhea, and
impaired or altered immune function (206). The ability of
the body to resist infectious diseases may be weakened, result-
ing in opportunistic infections. Certain mycotoxins, such as
zearalenone, have been found to cause infertility and still-
births in pigs (201). Low-level, complex exposures from a
mixture of mycotoxins, as would be typically encountered
in real-life situations, may have synergistic effects, which
may result in central neuroendocrine-immune changes and
TABLE 8 Some toxigenic fungi, fungal chemical metabolites, and their health effects
Fungi Chemical metabolites Health effects
Penicillium (>200 species) Patulin Hemorrhage of lung, brain disease
citrinin Renal damage, vasodilatation, bronchial constriction,
increased muscular tone
ochratoxin A Nephrotoxic, hepatotoxic
citroviridin Neurotoxic
emodin Reduced cellular oxygen uptake
gliotoxin Lung disease
verruculogen Neurotoxic: trembling in animal
secalonic acid D Lung, teratogenic in rodents
Aspergillus spp. Patulin Hemorrhage of lung, brain disease
A. clavatus Aflatoxin B1 Liver cancer, resp. cancer, cytochrome P-450
monooxygenase disorder.
A. flavus and A. parasiticus Sterigmatocystin Carcinogen
A. versicolor ochraceus Ochratoxin A Nephrotoxic, hepatotoxic
Stachybotrys chartarum,
Fusarium species,
Trichoderma species
Trichothecenes
a
(more than 50 derivatives
known): T-2, nivalenol, deoxynivalenol,
diacetoxyscirpenol, satratoxin H, G,
other macrocyclic trichothecenes
Spirolactone
Zearalenone
Immune suppression and dysfunction, cytotoxic,
bleeding, dermal necrosis; high dose ingestion = lethal
(human case reports); low dose, chronic = potentially
lethal); teratogenic, abortogenic (in animals).
Hemorrhage
“Alimentary toxic aleukia”(ATA) reported in Russia
and Siberia
“Staggering wheat”in Siberia
“Red mold disease”in Japan
Neurotoxic/nervous behavior abnormality
Co-carcinogen/chemotoxic (?)
Anticomplement function.
Phytoestrogen may alter immune function; stimulates
growth of uterus and vulva, atrophy of ovary
Claviceps spp. Ergot alkaloids Prolactin inhibitor, vascular constriction, uterus
contraction promoted.
a
Trichothecenes are also produced by Myrothecium, Trichothecium, and Gibberella (teleomorph of some Fusarium species).
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consequently in complex effects of the endocrine and nerv-
ous system (121).
Nonallergic complaints from patients in which myco-
toxin-producing fungal exposure was either confirmed or
strongly suggested include recurrent cold and flu–like symp-
toms, extreme fatigue, constant sore throat or skin irritation,
severe and unusual headaches, neuromuscular and neurocog-
nitive dysfunction (tremor and shakes, unusual memory and
concentration problems), bleeding disorders of the lung in
infants, irregular menses, diarrhea, dermatitis and irritation
of skin, and impaired immune function. Mycotoxins may
also be involved in occupational respiratory cancers among
food and grain workers (230), however, typical home or office
indoor environments have not been studied. Better con-
trolled studies are needed to improve our understanding of
mycotoxins found in the indoor environment and possible
adverse human health effects.
Historically, mycotoxins have been a problem to farmers
and food industries and in Eastern European and developing
countries (251). The large-dose exposure to fungi and myco-
toxins encountered by farmers and in food industries was gen-
erally considered unlikely to occur in nonfarming activities.
However, many toxigenic fungi, such as S. chartarum and spe-
cies of Aspergillus,Penicillium, and Fusarium have been found
to infest buildings with known indoor air and building-related
problems and illnesses (29,156,203,252). It has been sug-
gested that inhalation exposure to mycotoxin-containing
fungal spores is significant in the reported cases of building-
related mycotoxicoses (252). Croft et al. (203) reported sev-
eral cases of mycotoxicoses caused by airborne exposure to the
toxigenic fungus S. chartarum in a residential building. Addi-
tional cases of office building–associated Stachybotrys myco-
toxicosis were reported by Hodgson et al. (226), Johanning
(253), and Johanning et al. (156). Satratoxin H was detected
in the fungus isolated from the contaminated building. Hem-
orrhagic lung disease in infants was highly associated with
indoor S. chartarum exposure in a case cluster investigation
in Cleveland (254) and in a case-home investigation in
the U.S. Midwest (255). Subsequently consultants for the
Centers for Disease Control and Prevention called for more
research to prove the causal relationship of Stachybotrys
and idiopathic pulmonary hemorrhage in infants on review
of the Cleveland study (256). After more than 10 years,
more cases were reported, increasing from 9 cases in the orig-
inal study to 52 cases at present. Among the cases, 91% of
patients were living in residences with S. chartarum (257).
Studies with toxic Stachybotrys fungi in mice showed similar
effects (inflammation and hemorrhage) (258). S. chartarum
was isolated from brochoalveolar lavage fluid of a child
with pulmonary hemorrhage (259), and S. atra exposure
was found in an infant who developed laryngeal spasm and
hemorrhage during general anesthesia (260). In an epide-
miological study a high prevalence of pulmonary diseases
of office workers in Florida court buildings were reported
after prolonged indoor exposure to primarily S. chartarum
and A. versicolor (226).
Mycotoxins generally have low volatility; therefore, inha-
lation of volatile mycotoxins is not very likely (206). Rather,
the toxins are an integral part of the fungus. Sorenson et al.
(261) demonstrated in the laboratory that aerosolized conidia
of S. atra contained trichothecene mycotoxins. The most
common toxin was satratoxin H. Lesser amounts of satratoxin
G and trichoverrols A and B were also detected but less fre-
quently. They also found that most of the airborne particles
were within respirable range. Similar experiments, conducted
by Pasanen et al. (262), demonstrated that trichothecene
mycotoxins were in airborne fungal propagules of S. atra
and could be collected on membrane filters. Conidia of
A. flavus and A. parasiticus were reported to contain aflatoxins
(263). Miller (5) also reported detection of two mycotoxins,
deoxynivalenol and T-2 toxin, in conidia of Fusarium grami-
nearum and F. sporotrichioides, respectively. These references
suggest that inhalation exposure to conidia may also increase
the chance of exposure to mycotoxins. Corey et al. (123)
found that satratoxin G from S. chartarum induced rhinitis
and apoptosis of olfactory sensory neurons in the nasal airways
of rhesus monkeys.
Although relationships were established to link inhalation
exposure to mycotoxin-containing fungal spores and symp-
toms of mycotoxicoses in fungi-infested indoor environments
(155,203,261,262), other possible exposure routes such as
ingestion and skin contact are likely. Because fungal spores
are ubiquitous in a contaminated environment, the chance
of ingesting toxin-containing spores is likely to increase
through eating, drinking, and smoking. It is prudent to limit
exposure to such potent toxic chemicals (124), particularly
when significant fungal growth and amplification is found
indoors (134).
The toxigenic fungus frequently detected in “problem
buildings”is S. chartarum, which produces a series of potent
cytotoxins (trichothecenes, satratoxins, and spirolactones)
as well as a variety of other compounds affecting the immune
system (240,264,265). Case studies of health effects and
immunological laboratory changes related to indoor exposure
to trichothecenes and possibly other mycotoxins, disorders of
the respiratory and central nervous system were noted (215,
266,267). Abnormal test results of the cellular and humoral
immune system were found (152). In earlier cases in Eastern
Europe, typically in an agricultural setting, marked leukope-
nia or acute “radiation-mimetic”effects on the blood cell sys-
tem with subsequent sepsis-like opportunistic infections after
trichothecene ingestion were reported (268,269).
Trichothecenes are considered to be the most potent
small molecule inhibitor of protein synthesis, acting through
inhibition of the peptidyl transferase activity (219,270).
These toxins can cause alveolar macrophage defects and
may affect phagocytosis. They have been investigated for
use in cancer treatment (271), but also in chemical-biological
warfare. The presence of fungal chemical metabolites has
been reported in several cases of animal and human ingestion-
related mycotoxicosis, resulting sometimes in death (252,
272). Mycotoxins, such as satratoxin H of the trichothecene
group, have been shown to cause depressed Tor B lymphocyte
activity, suppressed immunoglobulin and antibody produc-
tion, reduced complement or interferon activity, and
impaired macrophage-effector cell function of human neutro-
phils (20).
Laboratory changes of immunoglobulins (IgA, IgE, IgG,
and IgM) in workers handling mycotoxin-contaminated
foodstuffs, primarily deoxynivalenol (vomitoxin), have
been reported (273). An increase of IgA production and
IgA nephropathy and a decrease of IgG and IgM after inges-
tion of vomitoxin were reported in a mice experiment (274).
Renal failure and IgG deposition in the glomeruli after inha-
lation of ochratoxin produced by Aspergillus ochraceus was
found in the case of a farmer (275).
A WHO task group concluded that an association
between trichothecene exposure and human disease episodes
is possible; however, only limited data are available (238).
Immunotoxicological effects principally depend on the expo-
sure conditions, dose, and timing. Some immunological
effects may only be transient, of short duration, and difficult
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to detect in routine medical tests. Medical findings are often
nonspecific and other systemic diseases or causes need to be
ruled out by the experienced clinician. The treating physician
often does not recognize mycotoxicosis, especially because
exposure circumstances and presence of certain mycotoxins
are unknown. Advanced fungal exposure characterization
and sampling techniques now available should improve the
chances for better medical detection of mycotoxicosis.
Analytical methods involving immunoassays and cell line
cytotoxicity analysis are able to provide relatively rapid and
easy screening tests to detect the presence of mycotoxins in
fungal-contaminated materials (157,250,276).
Mycotoxin research faces methodological challenges,
such as misidentification of mycotoxigenic fungi or using
sequences generated from misidentified cultures (22). This
may led to erroneous results, such as false negative or positive
results.
Volatile Organic Compounds Produced by Fungi
Fungi in active growth produce VOCs also known as
MVOCs, which typically are noticed as a musty, moldy
odor. Over 200 MVOC compounds have been identified
from different fungi (277). Indoor measured VOC levels,
however, are typically low and any serious health risks are
uncertain (278,279). Possibly, related mucous membrane
and olfactory irritations may trigger an “unpleasant odor reac-
tion”and annoyance. Measurement of VOCs may be an indi-
cator of excessive indoor fungal growth (280). A number of
VOCs have been identified from fungi common in indoor
contamination. Most of these fungal VOCs are derivatives
of alcohols, aldehydes, amines, ketones, terpenes, esters,
hydrocarbons, aromatics, and sulfur-containing compounds
(281,282). The in vitro production of fungal volatiles from
47 Penicillium taxa were made up of alcohols, ketones, esters,
small alkenes, monterpenes, sesquiterpenes, and aromates
(283). However, aldehydes were not detected.
Some of the fungal VOCs have an unpleasant odor (4),
and other fungi (such as mushrooms) produce VOCs of pleas-
ant odors and flavors. 1-Octen-3-ol, one of the major fungal
VOCs, has a characteristic mushroom odor. The musty,
moldy, and earthy odors are likely to come from 2-octen-1-ol
and geosmin (1,10-dimethyl-9 decalol) (4,29). Ezeonu et al.
(27) identified ethanol, 2-ethyl hexanol, cyclohexane, and
benzene from fiberglass air duct liners colonized by
A. versicolor,Acremonium obclavatum,andCladosporium her-
barum. Acetone and 2-butanone were only detected on agar
plate samples of A. versicolor and A. obclavatum. Other fungal
VOCs associated with two common indoor fungi, Penicillium
and Aspergillus, have been identified. They are 2-methyl-
isoborneol, 2-methyl-1-propanol, 3-methyl-1-butanol, and
3-octanone (4). Additional fungal VOCs are compiled and
listed by Ammann (25) and Batterman (26). Almost all of
the published information regarding fungal VOC’s concerns
Penicillium spp. and Aspergillus spp. Little is known about
VOCs of other common indoor fungal contaminants. A
recent study found MVOCs: anisole, 3-octanone, styrene,
3-methyl-anisole and 4-methyl-anisole emitted by S. charta-
rum (284).
CONCLUSIONS
Fungi, fungal spores, hyphae, and by-products are ubiquitous
in nature and in indoor environments. Although fungal
growth is found throughout nature, dampness and molds
should not be allowed in indoor environments such as homes,
offices, public buildings, and health care facilities. Fungi in
damp and water-damaged buildings play an important role
in public health and disease prevention. There is a growing
consensus among experts that fungi associated with dampness
leads to preventable health problems, primarily of the respira-
tory organs and allergies. They are allergenic and irritant/
toxic agents that typically cause or aggravate airways, or are
associated with infectious and mainly respiratory diseases in
exposed people. Research findings indicate that they are a
major problem in buildings where moisture control is poor
or where water intrusion is common. Human exposures in
these situations typically are a mixture of different fungi and
bacteria. Synergistic inhalation effects of fungal by-products,
such as mycotoxins in fungal spores, β-glucans, or likely fun-
gal MVOCs released into the surroundings are potentially
irritating, toxic, teratogenic, carcinogenic, and immune-
suppressive. Clinical diagnoses of mold allergies and fungal
infections are generally easier and less complicated than
emerging health concerns of such fungal metabolites as
(1-3)-ß-D-glucan, airborne mycotoxins, and fungal MVOCs.
Furthermore, risk assessment of human exposure to these
fungi and their by-products is complex, because multiple
agents, hypersensitivity reactions, and different disease out-
comes are involved. Human susceptibility to them varies
from individual to individual. Some of the health implica-
tions from inhalation exposure of fungi are undergoing further
research, particularly at low exposure concentrations that are
likely different from agricultural settings studied in the past.
In most cases, diligent exposure cessation and control leads
to symptom reversal and health improvement. Little is known
concerning the consequences of short-term and long-term
environmental exposures to mycotoxins and whether all of
the health effects are reversible. However, based on what is
known at present regarding fungal exposures and potential
adverse health effects, it is prudent to avoid or minimize expo-
sure to infectious, allergenic, and toxic fungi and to control
indoor growth conditions. Furthermore, fungal growth
indoors suggests water infiltration and damage to building
structures and material, that ought to be corrected to avoid
further decay.
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