1. Mold and Their Health Effects Edward J Peters, MD Austin Texas epeters@austinallergy.com

2. Fungi: Toxic Killers or Unavoidable Nuisances? Court finds insurer at fault in mold case $32 million awarded… The Austin American-Statesman, 6-2-2001

3. Austin American-Statesman 1-14-02

4. Fungi Filamentous organisms that absorb food from the environment after external digestion. Filamentous organisms that absorb food from the environment after external digestion. Cell walls are made of a variety of materials that carry some antigenicity. Cell walls are made of a variety of materials that carry some antigenicity. Most have a melanin pigment in the cell wall to protect from UV light. Most have a melanin pigment in the cell wall to protect from UV light. Glucans in the cell wall are endotoxin-like and irritating and stimulate the immune system. Glucans in the cell wall are endotoxin-like and irritating and stimulate the immune system.

5. Definition: “Molds” Common term for the multicellular fungi that grow as a mat of filaments. Common term for the multicellular fungi that grow as a mat of filaments. Familiar fungi: yeasts, rusts, smuts, mushrooms, puffballs, and bracket fungi. Familiar fungi: yeasts, rusts, smuts, mushrooms, puffballs, and bracket fungi. Exposure to fungi and their spores is unavoidable except in stringent air filtration and isolation situations (laminar flow units for bone marrow transplantation). Exposure to fungi and their spores is unavoidable except in stringent air filtration and isolation situations (laminar flow units for bone marrow transplantation).

6. Are Fungi Pathogenic? In healthy individuals, most fungi are not pathogenic. In healthy individuals, most fungi are not pathogenic. Superficial infections of the feet, groin, nails and skin are the most common “infection”. Superficial infections of the feet, groin, nails and skin are the most common “infection”. Limited number of fungi: Blastomyces, Coccidiodes, Cryptococcus, and Histoplasma can cause a severe illness in healthy individuals. Limited number of fungi: Blastomyces, Coccidiodes, Cryptococcus, and Histoplasma can cause a severe illness in healthy individuals.

7. Allergenic Substances All fungi produce some allergenic substances (enzymes) in the process of food digestion. All fungi produce some allergenic substances (enzymes) in the process of food digestion. Mycotoxins and antibiotics can be released into the environment during growth. Mycotoxins and antibiotics can be released into the environment during growth. 10% of the entire population and 40% of asthmatic patients are fungal-sensitive. 10% of the entire population and 40% of asthmatic patients are fungal-sensitive.

8. What do we know so far? Lots of “molds” are black. Lots of “molds” are black. Exposure is unavoidable. Exposure is unavoidable. Most fungi have never caused disease in humans. Most fungi have never caused disease in humans. Lots of people but not all are allergic to fungi. Lots of people but not all are allergic to fungi.

9. Indoor Levels of Fungi In a home without water intrusion, the levels of airborne fungi will be 40-80% of the outdoor levels. In a home without water intrusion, the levels of airborne fungi will be 40-80% of the outdoor levels. Outdoor concentrations vary widely by geographic area, season, atmospheric conditions (humidity, wind), and even time of the day. Outdoor concentrations vary widely by geographic area, season, atmospheric conditions (humidity, wind), and even time of the day. Verhoeff AP et al Allergy 1992; 47;83-91.

10. Sampling of Indoor Air: Problems No uniform numeric standards for indoor sampling data. No uniform numeric standards for indoor sampling data. No known dose-response relationship between a specific mold and any human health effects. No known dose-response relationship between a specific mold and any human health effects. Exposure to fungi occurs indoors as well as outdoors, thus there is no way to ascribe a health effect or sensitivity to any specific exposure or time period. Exposure to fungi occurs indoors as well as outdoors, thus there is no way to ascribe a health effect or sensitivity to any specific exposure or time period.

11. Indoor Ambient Air Fungal Concentrations In 820 residences without health complaints, indoor fungal counts averaged 1252 CFU/m 3 and outdoor were 1524 CFU/m 3. In 820 residences without health complaints, indoor fungal counts averaged 1252 CFU/m 3 and outdoor were 1524 CFU/m 3. In sawmills the airborne concentrations have been reported as high as 1.5 million CFU/m 3 without health effects reported. In sawmills the airborne concentrations have been reported as high as 1.5 million CFU/m 3 without health effects reported.

12. Respiratory Disease Caused by Fungi Allergic asthma and allergic rhinitis are the commonest problems. Allergic asthma and allergic rhinitis are the commonest problems. Allergic Fungal Diseases Allergic Fungal Diseases –ABPA: allergic bronchopulmonary aspergillosis –AFS: allergic fungal sinusitis Invasive Fungal Diseases Invasive Fungal Diseases –Immunocompromised hosts (bone marrow transplant recipients/diabetes)

13. Hypersensitivity Pneumonitis Results form the inhalation of significant quantities of fungal (or other) proteins. Results form the inhalation of significant quantities of fungal (or other) proteins. Occupational exposures are the most common cause. Malt Worker’s Lung (Aspergillus) and Cheese Washer’s Lung (Penicillium) are due to fungal proteins. Occupational exposures are the most common cause. Malt Worker’s Lung (Aspergillus) and Cheese Washer’s Lung (Penicillium) are due to fungal proteins. Characterized by acute febrile illness and pneumonitis. Characterized by acute febrile illness and pneumonitis.

14. HP Case Report 82-year-old female, hospitalized with acute RLL pneumonia, and symptoms cleared only to quickly return when she went home. 82-year-old female, hospitalized with acute RLL pneumonia, and symptoms cleared only to quickly return when she went home. Repeat chest X-ray 2 weeks later R and L lung infiltrates. Repeat chest X-ray 2 weeks later R and L lung infiltrates. Pulmonary function studies showed a FVC of 56% and FEV 1 of 58%. Pulmonary function studies showed a FVC of 56% and FEV 1 of 58%.

15. Hypersensitivity Pneumonitis

16. CT Scan Changes in HP

17. Hypersensitivity Pneumonitis Jacobs et al Ann Allergy Asthma Immunol 2002; 88:30

18. Did I lose you yet? All homes (buildings) have some fungi especially if there is some water intrusion. All homes (buildings) have some fungi especially if there is some water intrusion. No standard way to sample airborne fungi. No standard way to sample airborne fungi. Fungal diseases are either due to allergy or hypersensitivity in healthy people. Fungal diseases are either due to allergy or hypersensitivity in healthy people.

20. Sick Building Syndrome Poorly defined set of symptoms (often sensory) attributed to occupancy of a building. Poorly defined set of symptoms (often sensory) attributed to occupancy of a building. Investigations generally find no specific cause for the complaints. Investigations generally find no specific cause for the complaints. “Toxic Mold” (Stachybotrys) and its mycotoxins have been blamed but no causal relationship has been found. “Toxic Mold” (Stachybotrys) and its mycotoxins have been blamed but no causal relationship has been found.

21. Mycotoxins Metabolites from food digestion. Metabolites from food digestion. Aid the fungi compete for food by inhibiting growth of other organisms. Aid the fungi compete for food by inhibiting growth of other organisms. Low molecular weight and nonvolatile (not in air). Low molecular weight and nonvolatile (not in air). Health effects of mycotoxins comes from the animal or (rarely) human ingestion data, but not inhalation. Health effects of mycotoxins comes from the animal or (rarely) human ingestion data, but not inhalation. Penicillin and cyclosporine are examples of important “mycotoxins”. Penicillin and cyclosporine are examples of important “mycotoxins”.

22. Airborne Fungi in Buildings Highest fungal levels (indoors and outdoors) from 1,717 buildings were found in the Southwest region. Highest fungal levels (indoors and outdoors) from 1,717 buildings were found in the Southwest region. Most common culturable airborne fungi were Cladosporium, Penicillium, and Aspergillus. Most common culturable airborne fungi were Cladosporium, Penicillium, and Aspergillus. Stachybotrys chartarum was identified in the air of 6% of the buildings. Stachybotrys chartarum was identified in the air of 6% of the buildings. Shelton et al Appl Environ Microbiol 2002;68:1743-53.

23. Deuteromycete: Stachybotrys “Fatal Fungus” Spores are found worldwide on cellulose materials such as foam insulation, fiberboard, carpets, and even tobacco in cigarettes. Spores are found worldwide on cellulose materials such as foam insulation, fiberboard, carpets, and even tobacco in cigarettes. Mean concentration of 0.3 spores/m 3 in 2.9% of homes in southern California. Mean concentration of 0.3 spores/m 3 in 2.9% of homes in southern California. In all cases, Stachybotrys is only a minor component of the mycoflora. In all cases, Stachybotrys is only a minor component of the mycoflora.

24. Deuteromycete: Stachybotrys “Fatal Fungus” Slow-growing fungi that competes poorly with other rapidly growing fungi. Slow-growing fungi that competes poorly with other rapidly growing fungi. Recovered from air samples in 3-6% of surveys. Recovered from air samples in 3-6% of surveys. Saprophytic mold that grows on nonliving organic material (cellulose) in high humidity, and low nitrogen content. Saprophytic mold that grows on nonliving organic material (cellulose) in high humidity, and low nitrogen content. Stachybotrys is recovered from water damaged building surfaces, but in low concentrations compared to Pencillium and Aspergillus species. Stachybotrys is recovered from water damaged building surfaces, but in low concentrations compared to Pencillium and Aspergillus species. Terr AI. Ann Allergy Asthma Immunol 2001;87:S57-63.

25. Human Diseases Caused by Stachybotrys No case of a human systemic or local infection caused by any species of Stachybotrys. No case of a human systemic or local infection caused by any species of Stachybotrys. One case of asthma improving in a 4 year old who was lived in a home that had Stachybotrys in water-damaged carpet, but not in air samples. One case of asthma improving in a 4 year old who was lived in a home that had Stachybotrys in water-damaged carpet, but not in air samples. Possible toxicity to humans from ingestion of Stachybotrys exists as there are reports of horses dieing as the result of ingesting contaminated fodder in the 1930-1940’s in Russia. Possible toxicity to humans from ingestion of Stachybotrys exists as there are reports of horses dieing as the result of ingesting contaminated fodder in the 1930-1940’s in Russia.

26. Human Disease Caused by the Inhalation of “Killer Mold” In 1986, five family members and their maid suffered from “a variety of maladies”. These authors claimed that there was a trichothecene mycotoxin in the air which caused the illnesses. In 1986, five family members and their maid suffered from “a variety of maladies”. These authors claimed that there was a trichothecene mycotoxin in the air which caused the illnesses. Two additional reports of work exposure to a variety of molds, including S. atra, in 1996 and 1998 resulted in various non-specific complaints and a single case of “interstitial lung disease” based on history. Two additional reports of work exposure to a variety of molds, including S. atra, in 1996 and 1998 resulted in various non-specific complaints and a single case of “interstitial lung disease” based on history. Serum IgE and IgG to various fungi in all these cases were either negative or did not correlate with the exposures. Serum IgE and IgG to various fungi in all these cases were either negative or did not correlate with the exposures.

27. Acute Pulmonary Hemorrhage in Infants Geographic cluster of 10 cases between the ages of 1 and 8 months in Cleveland, OH in 1993-1994. Geographic cluster of 10 cases between the ages of 1 and 8 months in Cleveland, OH in 1993-1994. Successfully treated in the hospital, but recurred in five of the infants shortly after returning home. Successfully treated in the hospital, but recurred in five of the infants shortly after returning home. No other household members were effected. No other household members were effected. Most lived in older, water damaged housing and had household exposure to Stachybotrys and other molds. Most lived in older, water damaged housing and had household exposure to Stachybotrys and other molds.

28. “Killer Mold” is not a killer? Blamed for many problems (neurologic, memory, headaches) which have not been substantiated. Blamed for many problems (neurologic, memory, headaches) which have not been substantiated. “Killer Mold” is only rarely found in the air and its mycotoxins are not breathable. “Killer Mold” is only rarely found in the air and its mycotoxins are not breathable. The term “Toxic Mold” is misleading as many molds are toxic if you ingest them. The term “Toxic Mold” is misleading as many molds are toxic if you ingest them.

29. Does Mold Cause Asthma? 50% or more of homes of 4625 children reported dampness (molds, water damage, or water in basement). 50% or more of homes of 4625 children reported dampness (molds, water damage, or water in basement). Reported home dampness and mold is associated with “cough and wheezing”, but not clearly associated with asthma. Reported home dampness and mold is associated with “cough and wheezing”, but not clearly associated with asthma. Pulmonary Function Tests (FVC or FEV 1 ) were not effected by home dampness. Pulmonary Function Tests (FVC or FEV 1 ) were not effected by home dampness. Brunekreef et al Am Rev Respir Dis 1989; 140:1363

30. Household Mold Exposure in the First Year of Life 880 infants at high risk for asthma (sibling with asthma) were followed for the first 12 months of life. 880 infants at high risk for asthma (sibling with asthma) were followed for the first 12 months of life. Cladosporium (62%) and Penicillium (41%) were the most commonest fungi found in these homes. Cladosporium (62%) and Penicillium (41%) were the most commonest fungi found in these homes. Highest Penicillium levels (>1,000 CFU/m 3 ) were associated with wheeze and cough. Highest Penicillium levels (>1,000 CFU/m 3 ) were associated with wheeze and cough. Gent et al Environ Health Perspect 2002;110:A781-A786.

31. Effects of Indoor Fungi and Dust Mite Allergen Levels on Adults Bronchial hyperreactivity (BHR) and history of wheezing were evaluated in 485 adults who participated in the ECRHS. Bronchial hyperreactivity (BHR) and history of wheezing were evaluated in 485 adults who participated in the ECRHS. 77% of homes had levels of >10 μg/g dust mite allergen and 55% had airborne fungal counts >500 CFU/m 3. 77% of homes had levels of >10 μg/g dust mite allergen and 55% had airborne fungal counts >500 CFU/m 3. High levels of mold associated with BHR, but subsequent studies showed no relationship of levels of fungi (only “visible mold”) to Peak Flow. High levels of mold associated with BHR, but subsequent studies showed no relationship of levels of fungi (only “visible mold”) to Peak Flow. Dharmage et al Am J Repir Crit Care Med 2001;164:65-71. Dharmage et al Clin Exp Allergy 2002;32:714-20.

32. Perennial Allergens Dust Mite

33. Perennial Allergens German Cockroaches

34. Dust Mite Exposure in US Beds Dust mite allergen is a major risk factor for allergic sensitization and asthma. Dust mite allergen is a major risk factor for allergic sensitization and asthma. Measurable dust mite allergen was found in bed dust of 84% of 831 homes with children. Measurable dust mite allergen was found in bed dust of 84% of 831 homes with children. 46% had levels associated with allergies, and 24% had levels seen in asthma (>10 μg/g). 46% had levels associated with allergies, and 24% had levels seen in asthma (>10 μg/g). Older single family homes, musty odor, and high bedroom humidity predicted higher levels. Older single family homes, musty odor, and high bedroom humidity predicted higher levels. Arbes et al J Allery Clin Immunol 2003;111:408-14

35. Conclusion Fungi are a major component of the biosphere and adapt well to varying conditions, such as water-damaged building materials. Fungi are a major component of the biosphere and adapt well to varying conditions, such as water-damaged building materials. Mycotoxins are produced by most fungi and Stachybotrys is not unique in this regard. Mycotoxins are produced by most fungi and Stachybotrys is not unique in this regard. Stachybotrys remains a potential health risk, but human disease related to inhalation has not been established. Stachybotrys remains a potential health risk, but human disease related to inhalation has not been established. Furthermore, reports of subjective illnesses attributed to Stachybotrys are not compelling. Furthermore, reports of subjective illnesses attributed to Stachybotrys are not compelling.

36. Would you live in these homes?

37. American Academy of Pediatrics Recommendations 1. Prompt cleaning of water damaged areas with dilute bleach. 2. Parents of infants with Idiopathic Pulmonary Hemorrhage should be questioned about mold, but “testing of the environment for specific molds is usually not necessary”. 3. Pediatricians should be aware that there is no method to test humans for “toxigenic molds”. Pediatrics 1998;101:712-4

38. Do we have to destroy everything because of mold? No scientific studies support the need to destroy personal belongings or contents of rooms and buildings because they were in the environment. No scientific studies support the need to destroy personal belongings or contents of rooms and buildings because they were in the environment. Cleaning of the HVAC units with 0.25% Glutaraldehyde solution reduced fungi growth (CFU) for a least 8 weeks. Cleaning of the HVAC units with 0.25% Glutaraldehyde solution reduced fungi growth (CFU) for a least 8 weeks. Garrison et al Ann Allergy 1993;71:548-56.

39. Evaluation of Patient with “Toxic Mold” Symptoms Many patients are CERTAIN that mold exposure has caused the problem. Many patients are CERTAIN that mold exposure has caused the problem. Mold exposure “advocates” (physicians) have inappropriately promoted this idea. Mold exposure “advocates” (physicians) have inappropriately promoted this idea. A thorough evaluation often uncovers a pre-existing problem or underlying condition as the cause. A thorough evaluation often uncovers a pre-existing problem or underlying condition as the cause.

40. Evaluation and Work-up of “Mold Exposure” Comprehensive medical history and complete physical examination. Comprehensive medical history and complete physical examination. Obtain and review all prior pertinent medical records which can sometimes be voluminous. Obtain and review all prior pertinent medical records which can sometimes be voluminous. Laboratory evaluation may include a variety of tests depending on the type of complaint and exposure. Laboratory evaluation may include a variety of tests depending on the type of complaint and exposure.

41. Laboratory Testing in “Mold Exposure” CBC, chest x-ray, pulmonary function studies, and some testing for common allergens (skin testing or serologic testing) are usually necessary and indicated. CBC, chest x-ray, pulmonary function studies, and some testing for common allergens (skin testing or serologic testing) are usually necessary and indicated. Nasal smears, CT scan of the sinuses, and general chemistry screens are often obtained. Nasal smears, CT scan of the sinuses, and general chemistry screens are often obtained. Methacholine challenge for hyperreactivity can be very helpful when spirometry is normal. Methacholine challenge for hyperreactivity can be very helpful when spirometry is normal.

42. Role of Consultants in the Evaluation of “Mold Exposure” Indoor air quality assessment by a Certified Industrial Hygienist may be necessary especially in medical-legal evaluations. Indoor air quality assessment by a Certified Industrial Hygienist may be necessary especially in medical-legal evaluations. Rely on cultures of airborne fungi (CFU/m 3 ) and do not rely on spore counts or bulk specimens if you are trying to evaluate the health risk. Rely on cultures of airborne fungi (CFU/m 3 ) and do not rely on spore counts or bulk specimens if you are trying to evaluate the health risk.

43. Any Questions?