Dr. Jack D. Thrasher, PhD., Toxicologist, Immunotoxicologist, Fetal Toxicologist
Sandra L. Crawley, M.ED., LADC Trauma Specialist
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COMPLEXITY OF DAMP INDOOR SPACES
Section I: Introduction
The Committee on Damp Indoor Spaces completed its review of the literature published up to approximately October, 2003. This document is often cited as the authoritative source that molds (microbial) growth that occurs from water intrusion does not cause severe adverse health effects other than allergies and asthma in sensitized individuals. Note the cut off date of the literature review, October 2003. At the time of this writing it is February 8, 2008. Four plus years have since passed. The question that one must ask is how can a publication that is this outdated be authoritative? Actually, the Committee concluded in Table 5-12, page 212 the following:
“Inadequate or Insufficient Evidence to Determine Whether an Association Exists
Airflow Obstruction (in other wise healthy persons Skin Symptoms
Mucous membrane irritation syndrome Gastrointestinal tract problems
COPD Fatigue
Inhalation fevers (nonoccupational exposures) Neuropsychiatric symptoms
Lower respiratory illness in otherwise Healthy adults Cancer
Acute idiopathic pulmonary hemorrhage in infants Reproductive effects
Rheumatologic or other immune diseases”
Not included in the report were the following:
KH Kilburn, Editor. Molds and Mycotoxins. Heldref Publications, 2004
DC Straus, Editor. Sick Building Syndrome. Advances in Applied Microbiology, 2004.
Two recent reviews have appeared in the peer reviewed literature that point towards the fact that the indoor environment resulting from water intrusion is a complex issue. This environment cultivates molds, bacteria (gram negative and positive), protozoa and probably unrecognized other microorganisms. The microbial growth that occurs involves biological effects ranging from IgE allergies (skin, asthma) through chronic inflammation, toxic effects and probable infectious processes. The microbes release several potentially toxic by-products which include: hemolysins, mycotoxins, endotoxins, exotoxins, extracellular polysaccharides, glucans, galactomannans, proteolytic enzymes, particulates, and microbial volatile organic compounds (MVOCs), to mention a few. Coupled with the fact that people spend approximately 90 % of their time indoors, the issue of microbial growth and its by-products in the indoor environment should be top priority of Federal Agencies. Finally, the reader of this material will discover that one must determine the species of both mold and bacteria that are present in the indoor environment. The growth of indoor species is different than what occurs outdoors.LINKS:
The health effects of nonindustrial indoor air pollution
Clinical medicine and the budding science of indoor mold exposure.
Section II. INDOOR VS OUTDOOR MOLDS
We must remember that adults spend approximately 90 % of their time indoors and probably more for infants. Thus, the indoor climate and contamination is more important than outdoor. Also, Dr. Wallace of the U.S.E.P.A did air monitoring studies (TEAM) of humans and reported that humans have concentrations of xenobiotics in their expired breath that correlates with the air they breathe. In other words, if one is in a dry cleaning establishment picking up his/her garment, then the breath will contain chemicals associated with the cleaners. Same is true with respect to any type of indoor exposure, e.g. office or home.
When air sampling is done on a building (home or office) the testing laboratory will do outdoor mold spores as compared to indoor spores counts per cubic meter. Generally, it will be concluded that if the indoor concentrations are less than outdoors, a mold infestation of the building is not present. Another type of reporting that I have seen is that the indoor concentrations of mold spores do not exceed 300 spores per cubic meter; therefore a problem does not exist. Both concepts are not correct. There are no standards for concentrations of indoor and or outdoor mold spore counts. Also, outdoor counts are influenced by many factors: wind, temperature, time of day, recent rains, and frequency of watering shrubbery, backyard and front yard. Further, there is evidence that indoor concentrations of mold spores in contaminated building remain relatively constant. Finally, if one spends 90 % of his/her time (newborns and infants probably more) indoors, what do outdoor counts have to do with the exposure to indoor situations? Not much, according to the TEAM reports mentioned above.
Finally, you will see in the abstracts listed below that certain species of Aspergillus and Penicillium are amplified indoors vs outdoors. Thus, counts of Aspergillus/Penicillium spores in the indoor measurements are meaningless. One needs to determine the species indoors vs outdoors. This is best done by PCR DNA mold testing. In addition, since Stachybotrys chartarum spore counts are relatively rare outdoors, increased levels indoors is indicative of mold growth. Also, 50 % of the mold growth in the indoor environment is hidden in wall cavities and other places where they are not visible.LINKS:
Assessment of fungal contamination in moldy homes: comparison of different methods.
An indoor air quality study of an alligator (Alligator mississippiensis) holding facility.
Continually measured fungal profiles in sick building syndrome.
The roles of Penicillium and Aspergillus in sick building syndrome.
A method for detecting fungal contaminants in wall cavities.
Correlation between the prevalence of certain fungi and sick building syndrome.
Association of early-onset otitis media in infants and exposure to household mould.
Specific fungal exposures, allergic sensitization, and rhinitis in infants.
Mold infestation of wet spray-applied cellulose insulation.
Section III. Bacteria and Protozoa in Damp Indoor Spaces
Bacteria and Protozoa have been isolated and identified as contaminants in damp indoor spaces. These organisms have been ignored by both the media and medical profession in favor of the more popular phrases “Black Mold and Toxigenic Mold” as well as arguments regarding allergic vs nonallergic (toxic effects) of mold exposure. However, considerable research and publication of peer reviewed papers have been done. The protozoa consist of amoebae and ciliates. The amoebae interact with molds and bacteria leading to either enhancement or inhibition of other microbial growth. The bacteria have been shown to belong to both gram negative and gram positive groups. The gram negative are potential pathogens and release endotoxins (see Section IV) into the indoor environment. The gram positive bacteria are multiple with the actinobacter receiving the most attention. Three genera of the actinobacter are potentially dangerous. For example, Streptomyces and Nocardiopsis species release toxins that are considered as toxic if not more so than trichothecenes. Streptomyces californicus spores are less than one micron and have been shown to cause proinflammatory conditions in of the lungs in mice. The genus, Mycobacterium, can cause lung disease, e.g. Hot Tub Fever, hypersensitivity pneumonitis and other respiratory diseases. Pertinent abstracts on various aspects of these microbial contaminants are reproduced below.
LINKS:
Amylosin from Bacillus amyloliquefaciens, a K+ and Na+ channel-forming toxic peptide containing a polyene structure.
Mycobacteria and fungi in moisture-damaged building materials.
Toxic-metabolite-producing bacteria and fungus in an indoor environment.
Bacteria, molds, and toxins in water-damaged building materials.
Amoebae and other protozoa in material samples from moisture-damaged buildings.
Mycobacterial Aerosols and Respiratory Disease
Viability of fungal and actinomycetal spores after microwave radiation of building materials.
Toxic-metabolite-producing bacteria and fungus in an indoor environment.
Section IV. ENDOTOXINS AND RESPIRATORY INFLAMMATION
Endotoxins are lipopolysaccharides (LPS) that are in the outer cell wall of gram negative bacteria; examples of these bacteria are E. coli, Salmonella, Shigella, Pseudomonas, Neisseria, Bordetella. LPS are shed into the environment when the bacteria die. If an infectious state occurs and LPS are in the blood as condition called endotoxemia can occur. Endotoxemia can lead to septic shock and death.
Briefly, the immune mechanisms following inhalation of endotoxins leads to the release of proinflammatory cytokines and nitric oxide. In humans, LPS binds to the lipid binding protein (LBP) in the serum and transfer to CD14 on the cell membrane of immune cells; macrophages; monocytes; Langerhan cells, hepatocytes; microglia, among others. The bound LPS are then transferred to TLR4 receptors which initiates a signaling cascade of proinflammatory cytokines and nitric oxide. The CD14 receptors on microglia are believed to be in neurological diseases, e.g. Alzheimer’s, Parkinsonism. If you wish more information on LPS it is suggested that you consult a text book of Bacteriology. The proinflammatory cascade and the role of CD14 in neurological diseases can be found by searching the National Library of Medicine via Entrez PubMed.
The first two papers listed below by Martinez and Simpson et. al. clearly demonstrate that there is an interaction between genetic polymorphism of the CD14 gene and endotoxins for wheeze in nonatopic children and also for high vs low concentrations of indoor endotoxins. The third paper by Rao, et. al. demonstrates that both endotoxins and mold related glucans are increased in concentrations inside of homes following the Katrina hurricane. The concentrations were sufficient to cause illness in the occupants of the damaged homes. The remaining abstracts are devoted to proinflammatory respiratory conditions and Parkinsonism.
Mold related glucans and galactomannans are covered in Section V.LINKS:
CD14, endotoxin, and asthma risk: actions and interactions.
Endotoxin exposure, CD14, and allergic disease: an interaction between genes and the environment.
Endotoxin-induced lung inflammation is independent of the complement membrane attack complex.
Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by healthy volunteers.
Inter- and intraindividual variation of endotoxin- and beta(1 --> 3)-glucan-induced cytokine responses in a whole blood assay.
Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid.
Biomonitoring for assessment of organic dust-induced lung inflammation.
Inhalation toxicology models of endotoxin- and bioaerosol-induced inflammation.
Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses.
Effects of cytokines and infections on brain neurochemistry.
Section V. 1-3-BETA-GLUCANS
1-3-beta glucans (glucans) are polyglucose molecules found the cell wall of molds, some gram negative bacteria and plants. When molds die the glucans are released into the indoor environment. The glucans are immune modulators and the interactions with the adaptive and innate immune systems are complex. Nevertheless, the glucans are irritating to the mucous membranes. It appears that children are susceptible to their adverse health effects that are adults. Interestingly, exposure to glucans increases circulating lymphocytes and have been isolated from bronchoalveolar lavage fluid in individuals with acute eosinophilic pneumonia. The glucans probably up regulation of some parts of the inflammatory/immunological system due to mold exposure.LINKS:
Effects after inhalation of (1-->3)-beta-D-glucan and relation to mould exposure in the home.
Effects after inhalation of (1-->3)-beta-D-glucan in healthy humans.
Mould exposure at home relates to inflammatory markers in blood.
Inhalation of (1-->3)-beta-D-glucan causes airway eosinophilia.
Airways inflammation and glucan in a rowhouse area.
(1-->3)-beta-D-glucan and endotoxin modulate immune response to inhaled allergen.
Indoor Air-Related Effects and Airborne (1---3)-beta-d-Glucan
(1-->3)-beta-D-glucan - relationship to indoor air-related symptoms, allergy and asthma.
(1-->3)-beta-D-glucan and endotoxin in house dust and peak flow variability in children
SECTION VI. MICROBIAL FRAGMENTS IN THE INDOOR AIR
Particulates released from microbial growth in the indoor environment range from extremely small fragments (nanoparticles) through several microns (mycelial fragments and spores). Typical spore sizes of molds are 2-3.5 microns (A. versicolor); 2-3 X 4-7 microns (C. cladosporioides) and 5-6 microns (P. melinii). Highly respirable particles (propagules) less than the size of spores have been demonstrated to be present in the indoor environment. They are released in higher numbers (up to 320 times) than are spores and are in the range of 0.3 to 1.2 microns. The propagules are immunogenic, thus they contain antigens of various types. They are shed by normal human activity (walking, dancing, door slamming, music, etc.) that sets up vibrations between 1-20 Hz as well as high air velocity. Recent published papers revealed that trichothecene mycotoxins of S. chartarum, as well as other genera of mold, are present in these propagules as well spores and mycelial fragments in contaminated homes and buildings. In addition, symptomatic individuals occupying these structures have these mycotoxins in their sera when compared to controls, demonstrating exposure has occurred. Two additional studies listed below are confirmatory that by-products of S. chartarum are present in the sera of exposed individuals. Van Emon et. al. reported the detection of the hemolysin, stachylysin in the sera of five adults exposed to S. chartarum. Similarly, Yike et. al. found satratoxin-albumin adducts in the sera of animals and humans. Finally, Bloom et. al. utilizing mass spectrometry detected trichothecenes and sterigmatocystin in settled dust and building materials from water-damaged buildings. The abstracts of these papers are listed below. As suggested by Gorny et al “future fungal spore investigations in buildings with mold problems should include the quantitation of fungal fragments.” Since it is recognized that S. chartarum does not readily shed spores, then why have trichothecenes, stachylysin and satratoxin-albumin adducts been detected in the sera of humans exposed to the organism? Perhaps, Drs. Gorny, Brasel, Van Emon, Yike and Bloom have discovered something ignored by many others.LINKS:
Fungal fragments as indoor air biocontaminants.
Filamentous microorganisms and their fragments in indoor air--a review.
ELISA measurement of stachylysin in serum to quantify human exposures to the indoor mold Stachybotrys chartarum.
Detection of trichothecene mycotoxins in sera from individuals exposed to Stachybotrys chartarum in indoor environments.
Aerosolization of particulate (1-->3)-beta-D-glucan from moldy materials.
Mycotoxin adducts on human serum albumin: biomarkers of exposure to Stachybotrys chartarum.
SECTION VIII. RESPIRATORY INFLAMMATION
This section is divided into A (Animal) and B (human) testing for pulmonary inflammatory responses to mold spores, mycotoxins, mold antigens and microbial growth present in water damaged homes and buildings. In general, the observed inflammatory response is not IgE (allergy) mediated. Pro-inflammatory cytokines are detected in nasal lavage fluid, bronchoalveolar lavage fluid and peripheral blood. This occurs in both animals and humans. Thus, animal models do predict what is occurring in humans exposed to microbial growth and its by-products in damp indoor spaces. The mold and bacteria studied in the animal models include Aspergillus, Penicillium, Stachybotrys, Streptomyces and Mycobacterium. Proteinases present in mold spores appear to be involved in the process. (See Sections IV, V and VII for endotoxins, glucans and EPS)
The human studies have involved challenges with Aspergillus fumigatus and reports on groups of individuals exposed to water-damaged structures containing microbial growth. In general, there is some evidence of TH2 (IgE) cytokines being produced. However, the preponderance of the data demonstrate TH1 (nonallergic) production of proinflammatory cytokines. Some studies show an alleviation of the inflammatory condition upon removal of the subjects from the affected environment, only to have it reappear upon re-exposure.
You are invited to read the materials supplied in this section in order to satisfy your own curiosity regarding nasal and pulmonary inflammation.