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Health Effects Attributed to Mold

The following EMLabP&K presentation by Dr. Harriet Burge discusses the health effects to relatively common mold growth in the indoor environment. The webinar conducted on 19 Jan 2016 provide insight on the types of immunological effects people can experience in commercial, residential, and industrial settings. Much of the health effects depend on the person's health and if their immunological system is compromised by disease or medication in the fight against disease. All homes and occupations where there are dusty conditions from organic materials should be evaluated for potential health effects from mold. The tests are relatively simple and the answers could be life saving.

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Health Effects Attributed to Mold

  1. 1. Heath Effects Attributed To Mold Harriet A. Burge,Ph.D. Will begin at 9:00 a.m. (PST). Participants will be in listen only mode. Download the PDF of this presentation (case sensitive): http://www.emlab.com/m/media/mold-health-effects-webinar.pdf
  2. 2. Continuing Education Units (CEUs) To receive a certificate of attendance, you must complete the survey after the webinar: •Click on the survey link in the “Thank you” email (sent 1 hour after this webinar). •Complete survey by this Friday, January 22, 2016. •You will receive an email in 2-3 weeks with instructions when your certificate is ready. Copyright © 2016 EMLab P&K. All rights reserved.2
  3. 3. Outline 1. The immune system and how it relates to fungal disease 2. Infection 3. Hypersensitivity a. Allergies b. Hypersensitivity pneumonitis 4. Toxicity Copyright © 2016 EMLab P&K. All rights reserved.3
  4. 4. Immune System Evolved to prevent infection Plays a fundamental role in hypersensitivity diseases Is damaged by some toxins Copyright © 2016 EMLab P&K. All rights reserved.4
  5. 5. Immune System (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.5 • Development of all cells of the immune system begins in the bone marrow with a blood-forming stem cell • Two broad categories of immune responses: the innate immune system and the adaptive immune system • Central to both categories: the ability to distinguish our own tissues (that need protection) from foreign invaders (that need to be attacked)
  6. 6. Innate Immune Responses Copyright © 2016 EMLab P&K. All rights reserved.6 • Rely on cells that require no additional “training” to do their jobs. These cells include neutrophils, monocytes, natural killer (NK) cells and a set of proteins termed the complement proteins. • Innate responses to infection occur rapidly and reliably. Even infants have excellent innate immune responses.
  7. 7. Adaptive Immune Responses Copyright © 2016 EMLab P&K. All rights reserved.7 • Involve T-cells and B-cells, two cell types that require “training” or education to learn not to attack our own cells. • The advantages of the adaptive responses are their long-lived memory and the ability to adapt to new germs.
  8. 8. Cells of the Immune System • A. Bone marrow: most of the cells of the immune system are produced here as immature or stem cells. • B. Stem cells: have the potential to differentiate and mature into the different cells of the immune system. • C. Thymus: An organ located in the chest that instructs immature lymphocytes (white blood cells) to become matureT- lymphocytes. Copyright © 2016 EMLab P&K. All rights reserved.8
  9. 9. Cells of the Immune System (cont’d) • D. B-Cells: These lymphocytes differentiate into plasma cells that produce immunoglobulins (antibodies). • E. Cytotoxic T-cells: lymphocytes that mature in the thymus and are responsible for killing infected cells. • F. Helper T-cells: lymphocytes that “help” other T-cells and B-cells to perform their functions. Copyright © 2016 EMLab P&K. All rights reserved.9
  10. 10. Cells of the Immune System (cont’d) • I. Neutrophils (Polymorphonuclear PMN Cell): rapidly ingest microorganisms and kills them. • J. Monocytes: develop into macrophages when they migrate to tissues. Copyright © 2016 EMLab P&K. All rights reserved.10
  11. 11. Immunoglobulins (Antibodies) Copyright © 2016 EMLab P&K. All rights reserved.11 • Proteins that bind specifically to a particular substance—an antigen. • All antibodies have the same overall structure • Each antibody molecule has a unique structure that enables it to bind specifically to its corresponding antigen. • Antibodies are produced by plasma cells in response to infection, immunization, or allergen exposure.
  12. 12. Antibodies The two arms of the Y- shaped antibody molecule contain the variable regions that form the two identical antigen-binding sites. The stem or constant region engages the effector mechanisms that antibodies activate to eliminate pathogens or release symptom-causing chemicals. Copyright © 2016 EMLab P&K. All rights reserved.12
  13. 13. Copyright © 2016 EMLab P&K. All rights reserved.13
  14. 14. Infection – Colonization Copyright © 2016 EMLab P&K. All rights reserved.14 • An infection occurs when a microbe enters the body and begins to reproduce. The microbe must: – Survive and multiply under local conditions (e.g. of temperature and pH) to establish itself in its new habitat – Successfully compete against the established indigenous microbial flora – Resist local defense mechanisms • Once established on a body surface, an organism is said to have colonized that site.
  15. 15. Infection • The invading microbe may – Remain dormant – Directly damage cells, or – Immune system can cause symptoms such as fever, as it tries to rid your body of the invader. Copyright © 2016 EMLab P&K. All rights reserved.15
  16. 16. Infection – Host Response Copyright © 2016 EMLab P&K. All rights reserved.16 • Usually begins with an inflammatory reaction, followed by a humoral or cell-mediated immune response. • Damage occurs due to swelling, increased fragility of tissues, formation of pus, scarring or necrosis. • Chronic intracellular infection may cause formation of fibrous nodules and a state of latency from which acute infection can be re-established at a much later stage.
  17. 17. Classification of Mycoses • The clinical nomenclatures used for the mycoses are based on the – (1) Site of the infection, – (2) Route of acquisition of the pathogen, and – (3) Type of virulence exhibited by the fungus. Copyright © 2016 EMLab P&K. All rights reserved.17
  18. 18. Classification Based on Site of Infection • Superficial, • Cutaneous, • Subcutaneous, • Systemic (deep) infections depending on the type and degree of tissue involvement and the host response to the pathogen. Copyright © 2016 EMLab P&K. All rights reserved.18
  19. 19. Mycoses Copyright © 2016 EMLab P&K. All rights reserved.19
  20. 20. Classification Based on Route of Acquisition • Exogenous or endogenous routes of entry – Airborne, cutaneous or percutaneous. – Endogenous infection involves colonization by a member of the normal flora or reactivation of a previous infection. Copyright © 2016 EMLab P&K. All rights reserved.20
  21. 21. Classification Based on Virulence Copyright © 2016 EMLab P&K. All rights reserved.21 • Primary pathogens can establish infections in normal hosts. • Opportunistic pathogens cause disease in individuals with compromised host defense mechanisms. • The primary pathogens have relatively well-defined geographic ranges; the opportunistic fungi are ubiquitous.
  22. 22. Fungal Infections • All require living spores for disease • Virulent agents do not grow indoors and disease depends on disturbance of outdoor reservoirs • Skin agents are probably not airborne • Opportunistic agents common in the environment Copyright © 2016 EMLab P&K. All rights reserved.22
  23. 23. Primary (Virulent) Mycoses • Able to cause infection in a normal host – Coccidioides immitis – Histoplasma capsulatum – Blastomyces dermatitidis – Paracoccidioides brasiliensis (South America) Copyright © 2016 EMLab P&K. All rights reserved.23
  24. 24. Virulent Infections Copyright © 2016 EMLab P&K. All rights reserved.24 • Histoplasmosis (Histoplasma capsulatum) – Wet soil enriched with bird droppings – Soil disturbance necessary for dissemination – Endemic in the Mississippi valley • Blastomycosis (Blastomyces dermatididis) – Similar to Histoplasma • Coccidioidomycosis (Coccidioides immitis) – Dry desert soils – Sandstorms
  25. 25. Virulent Fungal Infection Copyright © 2016 EMLab P&K. All rights reserved.25 • Traveling to an area where the causative fungus is common raises the risk for this infection. • Serious infections occur in those with a weakened immune system due to: – Anti-tumor necrosis factor (TNF) therapy – Cancer – Chemotherapy – Glucocorticoid medications (prednisone) – Heart-lung conditions – HIV – Organ transplant – Pregnancy (especially the first trimester)
  26. 26. Histoplasma capsulatum Copyright © 2016 EMLab P&K. All rights reserved.26 • Etiologic agent of the most common respiratory fungal infection affecting humans. • Lives in the soil, usually in association with large amounts of bird or bat droppings. • Widely distributed throughout the subtropial and tropical zones of the world. In North America, H. capsulatum is particularly associated with the Mississippi and Ohio River valleys.
  27. 27. Histoplasma capsulatum (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.27 • Exists in soil in a mycelial form • Tuberculate macroconidia (8 to 14µm in diameter) and microconidia (2-5 µm in diameter) are formed in the soil • Microconidia are likely the major source of infection due to their small size, making them readily airborne with soil disturbance, and able to penetrate to the small airways of mammalian lungs by inhalation.
  28. 28. Histoplasma capsulatum (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.28 • In the body, H. capsulatum converts to a yeast form. • Lung infection can occur after inhalation of airborne, microscopic fungal spores when soil is disturbed. • Many people who inhale the spores do not get sick. • Symptoms of histoplasmosis are similar to pneumonia, and the infection can sometimes become serious if it is not treated.
  29. 29. Histoplasmosis Copyright © 2016 EMLab P&K. All rights reserved.29 • Between 50% and 80% of people who live in areas where Histoplasma capsulatum is common in the environment will show evidence of having been exposed to the fungus at some point in their lifetime. In these areas, 10% to 25% of HIV-infected people will develop disseminated histoplasmosis. • There is a PCR assay for detection of H. capsulatum in soil. Previously, soil suspensions had to be inoculated into mice and (after 6 weeks or so) the liver and spleen cultured.
  30. 30. Blastomyces dermatitidis (Blastomycosis) Copyright © 2016 EMLab P&K. All rights reserved.30
  31. 31. Blastomyces dermatitidis (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.31 • Although long thought to be restricted to the North American continent, cases have been diagnosed in Africa, Asia and Europe in recent years. • Clinical and epidemiological evidence indicates that humans and lower animals contract blastomycosis from some source in nature. • However, the natural habitat of B. dermatitidis has yet to be clearly delineated, despite some reports of its isolation from soil.
  32. 32. Blastomycosis Copyright © 2016 EMLab P&K. All rights reserved.32 • A true systemic (endemic) mycosis. • Occurs mainly in immunocompetent hosts • Acquired by inhalation and usually remains a lung infection. • Cutaneous infection occurs with direct inoculation of the fungus into the skin. • Dissemination to other organs and systems may occur, especially in immunocompromised hosts.
  33. 33. Coccidioides immitis (Valley Fever) • This fungus resides in soil • Spores become airborne with disturbance (e.g., wind) Copyright © 2016 EMLab P&K. All rights reserved.33
  34. 34. • Coccidioides is thought to grow best in soil after heavy rainfall and then disperse into the air most effectively during hot, dry conditions. • Climate change may be affecting the number of Valley fever infections, as well as the geographic range of Coccidioides. Coccidioides immitis (Valley Fever) cont’d Copyright © 2016 EMLab P&K. All rights reserved.34
  35. 35. Coccidioides immitis (Valley Fever) cont’d Copyright © 2016 EMLab P&K. All rights reserved.35 • Symptoms are flu-like, nonspecific and often difficult to diagnose. • Most people who breathe in the spores don’t get sick. Usually, people who get sick will get better on their own within weeks to months, but some people will need antifungal medication. • Immunocompromised people are at higher risk for severe illness. • Responsible for laboratory related infections where the agent is handled.
  36. 36. Opportunistic Infections Copyright © 2016 EMLab P&K. All rights reserved.36 • Are a serious issue for the immune compromised: – AIDS – Organ transplants – Chemotherapy – Bone marrow transplants • Not normally an issue for people with competent immune systems
  37. 37. Opportunistic Mycoses • Candida albicans • Aspergillus • Zygomycetes (Rhizopus, Rhizomucor, Absidia, Mucor sp. • Cryptococcus neoformans and C. gattii Copyright © 2016 EMLab P&K. All rights reserved.37
  38. 38. Candida albicans Copyright © 2016 EMLab P&K. All rights reserved.38 • Candida is a resident organism in the human body. • Infections are of endogenous origin (not environmental) • Illnesses: – Thrush (mouth or throat) – Yeast infection (genital area) – Diaper rash (baby’s bottom) – Invasive candidaisis (bloodstream)
  39. 39. Candida albicans (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.39 • Thrush – Infants and the elderly – Chemotherapy patients – Patients with immunosuppressive disease • Diaper rash – Not always caused by Candida – Can occur in any baby if bottom remains wet
  40. 40. Candidiasis or Candidemia Copyright © 2016 EMLab P&K. All rights reserved.40 • You are more likely to get this invasive type of infection if you: – Are in the hospital's intensive care unit (ICU) – Have had recent surgery – Have a central line (catheter) – Have a weakened immune system
  41. 41. Candida Infection on The Internet Copyright © 2016 EMLab P&K. All rights reserved.41 • Some people with unexplained symptoms and having a little information about Candida believe that systemic candida infection has caused many different symptoms both physical and psychological. • Unfortunately, a few physicians have supported this opinion. • The key term is “believe.” There is no evidence for such associations.
  42. 42. Aspergillus Infection • All animals and many plants have highly efficient mechanisms to prevent themselves being infected by Aspergillus, and it is usually only when those mechanisms are defective in some way that Aspergillus can grow within the body. • Thus, this is a true opportunistic infection Copyright © 2016 EMLab P&K. All rights reserved.42
  43. 43. Invasive Aspergillosis Copyright © 2016 EMLab P&K. All rights reserved.43 • Invasive aspergillosis (true Aspergillus infection) is an important medical concern in immunocompromised patients • It is an airborne disease • The number of living spores required to initiate an infection is unknown, and probably varies with the individual’s immune status. • Millions of spores can be inhaled with no infection occurring in normal people.
  44. 44. Aspergillus Infection (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.44 • Inhaled conidia germinate into invading hyphae that penetrate the respiratory epithelium. • Aspergillus traits, including the production of pigment, antioxidants, proteases, adhesins, siderophores, and mycotoxins, are implicated as potential virulence factors. • These factors interact in the patient with depressed immunity to allow infection to occur.
  45. 45. Aspergillosis In General Copyright © 2016 EMLab P&K. All rights reserved.45 • Invasive aspergillosis – Invasive infection • Aspergilloma – colonization of “holes” in the lung parenchyma forming Aspergillus balls • Allergic bronchopulmonary aspergillosis – Colonization of the mucous lining the lungs of asthmatics. • Only invasive aspergillosis can be accurately called an infection.
  46. 46. Zygomycetes Copyright © 2016 EMLab P&K. All rights reserved.46 • Orders Mucorales and Entomophthorales include human pathogens • Entomophthorales infection is very rare • Members of the Mucorales that cause human disease: – Rhizopus (most common) – Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum have also been causal agents.
  47. 47. Zygomycosis Copyright © 2016 EMLab P&K. All rights reserved.47 • The spores are transmitted by – inhalation, – a variety of percutaneous routes, – ingestion of spores. • Opportunistic: Host risk factors include – Diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns.
  48. 48. Cryptococcus neoformans Copyright © 2016 EMLab P&K. All rights reserved.48 • C. neoformans v. grubii and v. neoformans have a worldwide distribution and are often found in soil that has been contaminated by bird excrement. • C. neoformans has been recovered from the ruins of Chernobyl and may be able to use radiation as an energy source. • Cryptococcus is a basidiomycete belonging to the order Tremelliales (jelly fungi). Basidiospores are formed during a brief mycelial stage, and are aerosolized, leading to possible inhalation exposure.
  49. 49. Cryptococcum neoformans Copyright © 2016 EMLab P&K. All rights reserved.49 • C. neoformans is an opportunistic fungus. Normal healthy people are rarely infected. • Infections are usually pulmonary, although with severe immunosuppression such as in AIDS patients, meningioencephalitis can occur. • Pulmonary cryptococcosis can be treated with antifungal drugs. • Central nervous system infections are very difficult to treat and are often fatal.
  50. 50. Cryptococcus gattii Copyright © 2016 EMLab P&K. All rights reserved.50 • Cryptococcus gattii, formerly known as Cryptococcus neoformans var gattii, is a tropical species, only recently reported in northeastern North America. • According to the CDC, from 2004 to 2010, 60 cases were identified in the U.S.: 43 in Oregon, 15 from Washington, and one each from Idaho and California. • About 52% of these were in immunocompromised patients.
  51. 51. Skin Infections • Microsporum, Epidermophyton, and Trichophyton – Athlete’s foot – Ringworm – Jock itch Copyright © 2016 EMLab P&K. All rights reserved.51
  52. 52. Infection – Cutaneous Copyright © 2016 EMLab P&K. All rights reserved.52 • Microsporum, Epidermophyton, and Trichophyton • Dermatophytes cause infections of the skin, hair and nails, obtaining nutrients from keratinized material. • Dermatophytes generally do not penetrate into living tissue, but remain in the keratinized layer of the skin • Common name for these infections include ringworm, jock itch, athlete’s foot, and others • Transmission is through direct contact with infected people and shed fungal materials.
  53. 53. Copyright © 2016 EMLab P&K. All rights reserved.53
  54. 54. Hypersensitivity Copyright © 2016 EMLab P&K. All rights reserved.54 • Immune responses to innocuous antigens that lead to symptomatic reactions upon re-exposure – Hypersensitivity: The state of heightened reactivity to antigen. – Hypersensitivity reactions are classified by mechanism: • Type I reactions involve IgE antibody triggering of mast cells; • Type II reactions involve IgG antibodies against cell surface or matrix antigens; • Type III reactions involve antigen:antibody complexes; • Type IV reactions are T cell-mediated.
  55. 55. Type I Hypersensitivity – Allergy Copyright © 2016 EMLab P&K. All rights reserved.55
  56. 56. Mast Cells Copyright © 2016 EMLab P&K. All rights reserved.56 • Large cells found in connective tissues throughout the body, most abundantly in the submucosal tissues and the dermis. • Contain large granules that store mediator molecules including histamine. • Have high-affinity Fcε receptors (FcεRI) that allow them to bind IgE monomers. • Antigen-binding to this IgE triggers mast-cell degranulation and mast-cell activation, • Producing a local or systemic immediate hypersensitivity reaction.
  57. 57. Ports of Antigen (Allergen) Entry • Intravenous: – General release of histamine • Intradermal – Local release of histamine • Inhalation, upper airway – Local release of histamine • Inhalation, lower airway – Local release of histamine • Gastrointestinal – Local release of histamine – Diffusion into blood stream Anaphylaxis Wheal and flare Allergic rhinitis Asthma Diarrhea, vomiting Urticaria, anaphylaxis Copyright © 2016 EMLab P&K. All rights reserved.57
  58. 58. Type I Hypersensitivity – Allergic Diseases • Diseases – Allergic rhinitis (hay fever) – Asthma – Anaphylaxis – Eczema (atopic dermatitis) – Allergic bronchopulmonary aspergillosis Copyright © 2016 EMLab P&K. All rights reserved.58
  59. 59. Exposure To Fungal Allergens Copyright © 2016 EMLab P&K. All rights reserved.59 • Exposure to fungal allergens is high, and sensitization is common (at least 10% of the population) • As with most allergens, low doses over a long period of time are likely needed for sensitization. Higher doses for symptoms. • Fungal sensitivity predisposes the patient to severe asthma.
  60. 60. Outdoor Aerosol Copyright © 2016 EMLab P&K. All rights reserved.60 Most fungal allergen exposure occurs outdoors
  61. 61. Cladosporium Growing in Condensation Copyright © 2016 EMLab P&K. All rights reserved.61
  62. 62. Fungal Colonization Copyright © 2016 EMLab P&K. All rights reserved.62 • Diseases – Allergic bronchopulmonary aspergillosis (mycosis) – Allergic Fungal Sinusitis • Background – ABPA: fungus colonizes mucous in the lung; Symptoms caused by immune response to the fungus – AFS: Fungus colonizes mucous in sinuses; Sinuses fill with fungal hyphae and thick mucous produced in response to the fungal allergens – Risk depends on having chronic asthma or rhinitis – Only a few fungi are involved
  63. 63. Evidence for Allergic Reactions Copyright © 2016 EMLab P&K. All rights reserved.63 • Asthma: – There is extensive evidence to document that exposure to fungi can precipitate asthma attacks, and may be involved in the initial development of asthma in some circumstances. • Childhood asthma studies • Work related asthma studies
  64. 64. Interesting Point • Asthma attack related to fungi on mouth guard (Glass et al., 2007) – If mouth guard is used only at school, the school environment could be blamed – If mold is found in a building, the tendency is to blame the mold for symptoms – Important to consider other possibilities, especially if only one person is affected. Copyright © 2016 EMLab P&K. All rights reserved.64
  65. 65. Type III and IV Hypersensitivity Copyright © 2016 EMLab P&K. All rights reserved.65 • Hypersensitivity pneumonitis (also called allergic alveolitis) is caused by a combination of type III and IV hypersensitivity responses • Exposure to antigen leads to production of specific IgG molecules. These are called precipitating antibodies. • Re-exposure to antigen leads to formation of antigen/antibody complexes that deposit in the alveoli (small sacs in the lung. • This is the Type III response
  66. 66. Hypersensitivity Pneumonitis Copyright © 2016 EMLab P&K. All rights reserved.66 In addition: • Early response to the antigen leads to an increase in neutrophils and mononuclear cells in the alveoli and small airways. • These cells release proteolytic enzymes, prostaglandins, and leukotrienes. The production and release of interleukins, cytokines, growth factors, and various other mediators from T lymphocytes and macrophages play important roles in hypersensitivity pneumonitis pathogenesis.
  67. 67. Pathophysiology Copyright © 2016 EMLab P&K. All rights reserved.67 • The subacute, or intermittent, form: – Produces well-formed granulomas, bronchiolitis with or without pneumonia, and interstitial fibrosis – This type (stage) can often be reversed by eliminating exposure • Chronic forms: – Display chronic interstitial inflammation and alveolar destruction (honeycombing) – There is no good treatment for this form, and continuing exposure can lead to death
  68. 68. Acute Symptoms • Fever • Chills • Fatigue • Breathlessness • Chest tightness • Cough Copyright © 2016 EMLab P&K. All rights reserved.68
  69. 69. Exposures Leading To Hypersensitivity Pneumonitis Copyright © 2016 EMLab P&K. All rights reserved.69 • Acute HP – Intense exposure to small particle organic dusts including small fungal spores. • Chronic HP – Low level exposure to small particle antigens over a long period.
  70. 70. Antigens Leading To HP Copyright © 2016 EMLab P&K. All rights reserved.70 • Compost HP • Malt worker lung • Peat moss HP Aspergillus Aspergillus clavatus Monocillium sp, Compost Moldy barley Penicillium citreonigrum Peat moss • Suberosis Penicillum frequentans Moldy cork dust • Maple bark HP Cryptostroma corticale Moldy wood bark • Wood pulp worker lung Alternaria species Moldy wood pulp • Wood trimmer lung Rhizopus species Moldy wood trimmings • Tree cutter lung Penicillium (3 species) Paecilomyces sp. Aspergillus niger Rhizopus sp. Aspergillus sp. Wood chips from living maple and oak tree • Dry rot HP Merulius lacrymans Moldy rotten wood • Sequoiosis Graphium species, Moldy wood dust
  71. 71. Antigens Leading To HP (Cont’d) Copyright © 2016 EMLab P&K. All rights reserved.71 • Japanese summer-type HP • Cheese washer lung Trichosporon cutaneum Pencillum casei Damp wood and mats Cheese casings P.roqueforti • Tobacco worker lung Aspergillus sp. Moldy tobacco • Greenhouse HP Aspergillus sp. Penicillium sp. Cryptostroma corticale Moldy soil • Esparto grass HP Aspergillus fumigatus Moldy esparto (used to produce ropes, canvas, sandals, mats, baskets, and paper paste) • Soy sauce brewer lung Aspergillus oryzae Fermentation starter for soy sauce
  72. 72. Copyright © 2016 EMLab P&K. All rights reserved.72
  73. 73. Toxic Fungal Metabolites Copyright © 2016 EMLab P&K. All rights reserved.73 • Toxic mainly to bacteria: Antibiotics • Toxic mainly to plants: Phytotoxins • Toxic to the animal kingdom and produced by macrofungi (mushrooms): Mushroom toxins • Toxic to the animal kingdom and produced by microfungi: Mycotoxins
  74. 74. Toxicosis Classification of Mycotoxins Copyright © 2016 EMLab P&K. All rights reserved.74 • Classification schemes tend to reflect the training of the person doing the categorizing. – Clinicians: classification by organ affected • hepatotoxins, nephrotoxins, neurotoxins, immunotoxins, etc – Cell biologists: mechanism of action • teratogens, mutagens, carcinogens, and allergens – Organic chemists: chemical structure • lactones, coumarins – Et cetera
  75. 75. Acute vs. Chronic Toxicosis Copyright © 2016 EMLab P&K. All rights reserved.75 • Acute toxicity – Adverse effects of a substance that result either from a single exposure or multiple exposures in a short space of time (usually less than 24 hours). • Chronic toxicity – Prolonged (repeated) exposure to a substance – Prolonged internal exposure because a substance remains in the body for a long time • Doses required for acute toxicity are generally much higher than those for chronic toxicity.
  76. 76. Is A Disease Caused By Mycotoxin Exposure? Copyright © 2016 EMLab P&K. All rights reserved.76 • Anecdotal evidence: Suspicion that mycotoxins have caused symptoms • Animal studies: Documentation that effects CAN occur in animals • Epidemiology: Association between exposure and disease; Dose/response information • Biological monitoring: Measurement of toxins or their metabolites or adducts in body fluids
  77. 77. Anecdotal Evidence Copyright © 2016 EMLab P&K. All rights reserved.77 • Many anecdotal reports of mycotoxin associated illness in the lay press – None supported by unbiased data – (Unfortunately) the courts accept these as indicating better than a 50/50 chance of a cause/effect relationship • A few anecdotal reports in the peer reviewed literature indicating the possibility of an association – Most admit that the association is not documented – The courts accept these as well
  78. 78. Animal Studies Copyright © 2016 EMLab P&K. All rights reserved.78 • Many reports of animal studies of mycotoxin effects. • Most seek to document mechanisms of action • Those attempting dose/response effects use very high doses (much higher than would be expected from environmental exposure except by ingestion. • Many of these studies are very well done, and indicate that mycotoxins are, in fact, toxic. • They do not establish a connection between exposure and disease.
  79. 79. Epidemiological Studies Copyright © 2016 EMLab P&K. All rights reserved.79 • Several epidemiological studies associate chronic mycotoxin exposure with cancer. These are all occupational. • One epidemiological study reported associations between Stachybotrys on walls of infant bedrooms and pulmonary bleeding in the infants. • The epidemiology in this study was improperly done, and the same organization (CDC) published an analysis of the former study, saying that the conclusions were not justified.
  80. 80. Biological Monitoring Copyright © 2016 EMLab P&K. All rights reserved.80 • Biological monitoring is commonly done in studies documenting ingestion of mycotoxins. Most of these are focused on whether or not particular populations are routinely exposed to mycotoxins in their food. • A few studies claim detection of mycotoxins in bodily fluids of people reporting airborne residential mycotoxin exposure. So far, these studies are not convincing, primarily because of bias.
  81. 81. Lower Respiratory Infections Copyright © 2016 EMLab P&K. All rights reserved.81 • Lower respiratory illness: – There is epidemiological evidence that children living in damp buildings have an increased incidence of lower respiratory infections. – These effects are separate from asthma, and don’t depend on sensitivity to the fungi, or to family history of allergies. – Some hypothesize that mycotoxins are involved, but no good evidence for this connection has appeared.
  82. 82. Anecdotal evidence: word of mouth, case studies Copyright © 2016 EMLab P&K. All rights reserved.83 Experimental evidence Epidemiological evidence Logic “proof” Types of Evidence
  83. 83. Fungal Irritants Copyright © 2016 EMLab P&K. All rights reserved.84 • Irritants (volatile organic compounds): – There is some evidence that these agents cause mucous membrane (eye, nose) irritation, and may lead to headaches. – Evidence so far is incomplete but there is no indication so far that these effects do not occur. – Neurological effects probably due to perception of odors
  84. 84. Evidence for Fungal-Associated Irritant Effects Anecdotal evidence: word of mouth, case studies Copyright © 2016 EMLab P&K. All rights reserved.85 Experimental evidence Epidemiological evidence Logic “proof”
  85. 85. Fungal Toxins • Diseases – Cancer – Immunosuppression – Neurological effects – Irritant effects • Background – All of these effects are related to ingestion of moldy food. – Cancer requires long term exposure; exposure cumulative – Other effects are immediate; exposures not cumulative – Inhalation very unlikely as an exposure route Copyright © 2016 EMLab P&K. All rights reserved.86
  86. 86. Fungus Mycotoxins Possible health effects Alternaria alternata Tenuazoic acid Nephrotoxic, hepatotoxic, hemorrhagic Aspergillus flavus, A. parasiticus Aflatoxins Mutagenic, carcinogenic, hepatotoxic Aspergillus fumigatus Fumitremorgens, gliotoxin Tumorgenic, cytotoxic Cladosporium sp. Epicladosporic acid Immunosuppressive Fusarium moniliforme Fumonisins Neuro, nephrotoxic and hepatotoxic, carcinogen Stachybotrys chartarum (atra) Satratoxins, verrucarins, roridins Immunosuppressive, hemotoxic, hemorrhagic Copyright © 2016 EMLab P&K. All rights reserved.87 Mycotoxins
  87. 87. Fungal Toxins – New Information • New information – Hundreds of publications on dietary mycotoxins, especially in underdeveloped countries. – No new publications that provide evidence for airborne mycotoxin exposure. – Stachybotrys conidia require air speeds 1,000 times higher than those that normally prevail in the indoor environment. (Tucker et al. 2007) Copyright © 2016 EMLab P&K. All rights reserved.88
  88. 88. Fungal Toxins (cont’d) • Toxic molds on the web – Many sites on the web claim that scientists are underreporting the dangers of toxic mold. – Position papers by major medical organizations are considered “biased”. – Expert witnesses are considered biased because they are paid for presenting their opinions. Copyright © 2016 EMLab P&K. All rights reserved.89
  89. 89. Fungal Toxins (cont’d) • Comments Copyright © 2016 EMLab P&K. All rights reserved.90 – Medical groups should not rely on reviews for position papers, only the published peer reviewed research literature. – Courts should not decide scientific relevance of scientific literature. Position papers are consensus documents of experts in the field, and should be considered authoritative. – Just because scientists are often defense witnesses does not mean they do not know the facts. Experts are hired because they do know the facts. These same experts would be used by the plaintiffs if the facts fit their cases. – The fact remains that the exposure models are relevant and there is no good evidence for mycotoxin inhalation disease
  90. 90. • Synergistic effects Copyright © 2016 EMLab P&K. All rights reserved.91 • Biomarkers, and background measurements of each – (note dietary mycotoxins as confounder) – (sensitivity of the marker) • Ochratoxin A: 0.011-0.1/A. carbonarius conidium
  91. 91. Evidence for Fungal-Associated Mycotoxin Effects (Inhalation) Anecdotal evidence: word of mouth, case studies Copyright © 2016 EMLab P&K. All rights reserved.92 Experimental evidence Only forAgriculture Logic “proof”
  92. 92. Toxicological References Copyright © 2016 EMLab P&K. All rights reserved.93 • Eduard W. 2009. Fungal spores: A critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting. CRITICAL REVIEWS IN TOXICOLOGY 39(10): 799-864 • Hardin BD, Robbins CA, Fallah P, Kelman BJ. 2009. The Concentration of No Toxicologic Concern (CoNTC) and Airborne Mycotoxins JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH- PART A-CURRENT ISSUES 72(9): 585-598
  93. 93. • Pasqualotto, AC. (Ed.) 2010 Chapter: Ben-Ami R, Kontoyiannis DP, 345-379 • Kim et al., Indoor Air 2007; 17: 153–163 • Pini et al.,2008 • Tucker et al., Indoor Air 2007; 17: 153–163 • Burr et al., 2007. Thorax;62:767–772. • Fisk et al., Indoor Air 2007; 17: 284–296 • Holck et al., 2007. Basic & Clinical Pharmacology & Toxicology 101, 455-458 • Iverson et al., 2007. Eur J Clin Microbiol Infect Dis 26:879–886 • Nucci & Anaissie, 2007. CLINICAL MICROBIOLOGY REVIEWS, 695–704 • Wang et al., 2007. Pediatr Allergy Immunol : 18: 441–447 • Park et al., 2008. Environ Health Perspect 116:45–50. • Glass et al., 2007. Gen Dent. 55(5):4a36-40 • Sautour et al., 2007. J Hosp Infect. Dec;67(4):367-73. • Wicklow & Shotwell., 1983. Canadian J Microbiology. 29(1):1-5. Copyright © 2016 EMLab P&K. All rights reserved.94 General References
  94. 94. General References (cont’d) Copyright © 2016 EMLab P&K. All rights reserved.95 • Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: Hypersensitivity diseases. Available from: http://www.ncbi.nlm.nih.gov/books/NBK27136/ • http://www.niaid.nih.gov/topics/microbes/documents/microbesbook.pdf
  95. 95. Continuing Education Units (CEUs) To receive a certificate of attendance, you must complete the survey after the webinar: •Click on the survey link in the “Thank you” email (sent 1 hour after this webinar). •Complete survey by this Friday, January 22, 2016. •You will receive an email in 2-3 weeks with instructions when your certificate is ready. Copyright © 2016 EMLab P&K. All rights reserved.96
  96. 96. Thank you for your time! Copyright © 2016 EMLab P&K. All rights reserved.100 Questions about Mold: DGallup@emlabpk.com All other questions: webinars@emlabpk.com
  97. 97. Appendix EMLab P&K
  98. 98. EMLab P&K Products Authorized Distributorfor: Copyright © 2016 EMLab P&K. All rights reserved.99 Buy equipment and supplies for sampling allergens, asbestos, bacteria, mold, fungi, and more Shop online at www.emlab.com/store
  99. 99. Locations Nationwide to Serve You (Addresses on Following Slides) WASHINGTON OREGON IDAHO NEVADA MONTANA WYOMING UTAH ARIZONA COLORADO NEW MEXICO TEXAS NORTH DAKOTA SOUTH DAKOTA NEBRASKA KANSAS OKLAHOMA MINNESOTA IOWA MISSOURI ARKANSAS LOUISIANA WISCONSIN INDIANA ILLINOIS OHIO KENTUCKY TENNESSEE GEORGIA SOUTH CAROLINA NEWYORK PENNSYLVANIA MICHIGAN MAINE WEST VIRGINIA VIRGINIA NORTH CAROLINA NEW HAMPSHIRE VERMONT MARYLAND RHODEISLAND CONNECTICUT NEWJERSEY DELAWARE MASSACHUSETTS HAWAII Copyright © 2016 EMLab P&K. All rights reserved.100
  100. 100. EMLab P&K Locations Near You MicroLabs in bold are AIHA Accredited as documented by the Scope of Accreditation Certificate. Arizona - Phoenix 1501 West KnudsenDrive Phoenix, AZ 85027 phone: 800.651.4802 fax: 623.780.7695 AIHA LAP, LLC EMLAP# 102297 California - San Francisco 6000 Shoreline Ct, Suite 205 So. San Francisco, CA94080 phone: 866.888.6653 fax: 650.624.5371 AIHA LAP, LLC EMLAP# 102856 New Jersey - Marlton 3000 Lincoln Drive East, SuiteA Marlton, NJ 08053 phone: 866.871.1984 fax: 856.334.1040 AIHA LAP, LLC EMLAP# 103005 M I C R O L A B S L A B O R A T O R I E S California - San Diego 8304 Clairemont Mesa Blvd. Suite 103 San Diego, CA 92111 Phone: 866.465.6653 Colorado - Denver 4955 YarrowStreet Arvada, CO 80002 phone: 800.651.4802 Florida - Ft.Lauderdale 6301 NW 5th Way Suite 1410 Ft. Lauderdale, FL33309 phone: 877.711.8400 Georgia - Atlanta 6500 McDonough Dr. Suite C-10 Norcross, GA30093 phone: 877.711.8400 Illinois - Chicago 1815 West DiehlRd. Suite 800 Naperville, IL 60563 phone: 866.871.1984 Nevada - Las Vegas 6000 S. Eastern Ave. Suite 5E Las Vegas, NV 89119 phone: 866.888.6653 California -Glendale 1010 N. Central Ave. Suite 390 Glendale, CA 91202 phone: 866.465.6653 California -Irvine 17461 Derian Ave. Suite 100 Irvine, CA 92614 Phone: 866.465.6653 California -Sacramento 880 Riverside Parkway West Sacramento, CA95605 phone: 866.888.6653 Texas - Houston 6310 Rothway St. Houston, Texas 77040 phone: 800.651.4802 Virginia - Fairfax 3929 Old Lee Highway Unit 91C Fairfax, Virginia 22030 phone: 866.871.1984 Washington -Seattle 19515 North Creek Parkway N, Suite 100 Bothell, WA98011 phone: 866.888.6653 For the most current list of locations, please visit us at www.emlab.com Contact individual laboratories for service capabilities and scopes of accreditation. Copyright © 2016 EMLab P&K. All rights reserved.101
  101. 101. TestAmerica Locations For the most current list of locations, please visit us at www.emlab.com For your convenience, you can drop off samples for EMLab P&K at these locations. CALIFORNIA- Pleasanton 1220QuarryLn. Pleasanton,CA94566 phone:(925)484-1919 CALIFORNIA- SanBernardino 202E.Airport Road Suite140 SanBernardino,CA92408 Phone:(909)370-4707 CALIFORNIA–W.Sacramento 880RiversidePkwy WestSacramento,CA95605 phone:(916)373-5600 CONNECTICUT 128LongHill CrossRd. Shelton,CT06484 phone:(203)929-8140 FLORIDA- Jacksonville 8933WesternWay,Suite 1 Jacksonville,FL32256 phone:(904)519-9551 FLORIDA-Orlando 8010SunportDrive, Suite116 Orlando,FL32809 phone:(407)851-2560 FLORIDA- Pensacola 3355McLemoreDr. Pensacola,FL32514 phone:(850)474-1001 FLORIDA - Tallahassee 2846 Industrial Plaza Dr. Tallahassee,FL32301 phone:(850)878-3994 FLORIDA-Tampa 6712BenjaminRd.,Suite 100 Tampa,FL33634 phone:(813)885-7427 GEORGIA-Atlanta 6500McDonoughDrive, SuiteC-10 Norcross,GA30093 phone:(678)966-9991 GEORGIA- Savannah 5102LaRocheAvenue Savannah,GA31404 phone:(912)354-7858 HAWAII- Honolulu 99-193AieaHeightsDr. Suite121 Aiea,HI96701 phone:(808)486-5227 ILLINOIS-Chicago 2417BondStreet UniversityPark,IL60484 phone:(708)534-5200 ILLINOIS-Elmhurst 655W.GrandAve.,Suite 205 Elmhurst,IL60126 phone:(630)758-0262 INDIANA- Indianapolis StutzBusinessCenter 212W.10thStreet,SteA-205 Indianapolis,IN46202 Phone:(317)264-9686 INDIANA-Valparaiso 2400CumberlandDrive Valparaiso,IN46383 phone:(219)464-2389 IOWA-CedarFalls 704EnterpriseDrive CedarFalls,IA50613 phone:(319)277-2401 IOWA-Davenport 736FederalSt.,Suite 2202 Davenport,IA52803 phone:(563)323-7944 LOUISIANA-Baton Rouge 6113BenefitDr. BatonRouge,LA70809 phone:(225)755-8200 MARYLAND -Baltimore 5710ExecutiveDrive,Suite 106 Baltimore,MD21228 phone:(410)869-0085 MASSACHUSETTS-Boston 240BearHill Rd.,Suite 104 Waltham,MA02451 phone:(781)466-6900 MASSACHUSETTS-Westfield 53SouthamptonRoad Westfield,MA01085 phone:(413)572-4000 MICHIGAN- Brighton 10448Citation Drive, Suite200 Brighton,MI48116 Phone:(810)229-2763 MINNESOTA- Minneapolis 7204 West27thStreet,Suite114 St. LouisPark,MN55426 phone: (800)593-8519 ALABAMA-Mobile 900LakesideDrive Mobile,AL36693 phone:(251)666-6633 ALASKA -Anchorage 2000W.International Airport Rd.,SuiteA10 Anchorage,AK99502 phone:(907)563-9200 ARIZONA- Phoenix 4625E.CottonCenterBlvd., Suite189 Phoenix,AZ85040 phone:(602)437-3340 ARIZONA- Tucson 1870W.PrinceRoad,Suite 59 Tucson,AZ85705 phone:(520)807-3801 CALIFORNIA–CostaMesa 3585CadillacAve,SuiteA CostaMesa,CA92626 phone:(714)258-8610 Copyright © 2016 EMLab P&K. All rights reserved.102
  102. 102. TestAmerica Locations (cont’d) NEWYORK-Albany 25KraftAve. Albany,NY12205 phone:(518)438-8140 NEWYORK-Buffalo 10HazelwoodDrive, Ste. 106 Amherst,NY14228 phone:(716)691-2600 NEWYORK-NewYorkCity 47-3232ndPlace,Suite1141 LongIslandCity, NY11101 Phone:(347)507-0579 NEWYORK-Syracuse 118BossRd. Syracuse,NY13211 phone:(315)431-0171 NORTHCAROLINA-Charlotte I-85SouthBldg. 2858QueenCity Dr.,SuiteB Charlotte,NC28208 phone:(704)392-1164 NORTHCAROLINA- Raleigh 101-FWoodwindsIndustrial Court Cary,NC27511 phone:(919)380-9919 For the most current list of locations, please visit us at www.emlab.com For your convenience, you can drop off samples for EMLab P&K at these locations. OHIO- Cincinnati 11416ReadingRoad Cincinnati, OH45241 phone:(513)733-5700 OHIO- Dayton 4738GatewayCircle Dayton,OH45440 Phone:(937)294-6856 OHIO- NorthCanton 4101ShuffelStreetNW NorthCanton,OH44720 phone:(330)497-9396 OREGON-Portland 9405 SWNimbusAvenue Beaverton,OR97008 phone:(503)906-9200 PENNSYLVANIA-KingofPrussia 1008W.Ninth Ave. KingofPrussia,PA19406 phone:(610)337-9992 PENNSYLVANIA-Pittsburgh 301AlphaDrive Pittsburgh,PA15238 phone:(412)963-7058 SOUTHCAROLINA- Charleston 1436-ANorthPointLane Mt.Pleasant,SC29464 phone:(843)849-6550 TENNESSEE-Knoxville 5815MiddlebrookPike Knoxville,TN37921 phone:(865)291-3000 TENNESSEE-Nashville 2960FosterCreightonDr. Nashville, TN37204 phone:(615)726-0177 TEXAS -Austin 14050SummitDr.,Ste.A100 Austin,TX78728 phone:(512)244-0855 TEXAS-Beaumont 4400LawndaleAve. Groves,TX77619 phone:(409)540-5302 TEXAS-CorpusChristi 1733N.PadreIslandDrive CorpusChristi, TX78408 phone:(361)289-2673 MISSOURI- Eureka 1699WestFifthStreet, #200 Eureka,MO63025 Phone:(314)302-8354 MISSOURI- KansasCity 601NW39thStreet BlueSprings,MO64015 phone:(800)276-1286 MISSOURI -St.Louis 13715RiderTrailNorth EarthCity, MO63045 phone:(314)298-8566 NEW JERSEY - Edison 777 NewDurham Road Edison,NJ08817 phone:(732)549-3900 NEWJERSEY-SouthJersey 520FellowshipRd.,SuiteA-106 Mt.Laurel,NJ08054 phone:(856)222-1990 TEXAS -SanAntonio 404E.Ramsey,Suite208 SanAntonio,TX78216 phone:(210)344-9751 VERMONT -Burlington 30CommunityDrive, Suite11 SouthBurlington,VT05403 phone:(802)660-1990 VIRGINIA-VirginiaBeach 5135ClevelandStreet VirginiaBeach,VA23462 phone:(757)671-1291 WASHINGTON-Richland 2800GeorgeWashingtonWay Richland,WA99354 phone:(509)375-3131 WASHINGTON-Spokane 11922E.1stAve. Spokane,WA99206 phone:(509)924-9200 WASHINGTON- Tacoma 57558thStreetEast Tacoma,WA98424 phone:(253)922-2310 Copyright © 2016 EMLab P&K. All rights reserved.103
  103. 103. When quality and accuracy are critical. Copyright © 2016 EMLab P&K, a TestAmerica Company Analytical Services: Fungi, Asbestos, Bacteria, USP <797>, PCR, Allergens & Radon Phone: (866) 888-MOLD (6653) Email: info@emlabpk.com Web: www.emlabpk.com

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The following EMLabP&K presentation by Dr. Harriet Burge discusses the health effects to relatively common mold growth in the indoor environment. The webinar conducted on 19 Jan 2016 provide insight on the types of immunological effects people can experience in commercial, residential, and industrial settings. Much of the health effects depend on the person's health and if their immunological system is compromised by disease or medication in the fight against disease. All homes and occupations where there are dusty conditions from organic materials should be evaluated for potential health effects from mold. The tests are relatively simple and the answers could be life saving.

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