Indoor Molds

Stachybotrys: A risk factor for pulmonary hemorrhage/hemosiderosis?

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Stachybotrys: A risk factor for pulmonary hemorrhage/hemosiderosis?

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An increase in the number of cases of acute pulmonary hemorrhage/hemosiderosis in infants from 3 cases during 1983-1993 to 8 cases during January 1993-November 1994 at a hospital in Cleveland, Ohio led to a case-control study of the risk factors for the disease. The study results indicated that acute pulmonary hemorrhage/hemosiderosis was associated with increased levels of measurable household fungi (including Stachybotrys chartarum) among other factors.

More information available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/00033843.htm: CDC. Acute Pulmonary Hemorrhage/Hemosiderosis Among Infant--Cleveland, January 1993 – November 1994. MMWR. 1994;43:881-3.
http://www.cdc/gov/mmwr/preview/mmwrhtml/00045680.htm: CDC. Update: Pulmonary Hemorrhage/Hemosiderosis Among Infants—Cleveland, Ohio, 1993-1996. MMWR. 1997;46:33-5.

An internal CDC committee as well as an external group of experts reviewed the original CDC case-control study conducted on the acute pulmonary hemorrhage/hemosiderosis in infants and the original report generated from the study data. The committees concluded the following:

“The reviews led CDC to conclude that a possible association between acute pulmonary hemorrhage/hemosiderosis in infants and exposure to molds, specifically Stachybotrys chartarum, commonly referred to by its synonym Stachybotrys atra, was not proven.”

The groups site 3 factors as the basis for their conclusion.

1. The Odds Ratio (OR) was inflated.
   - incorrect calculation of airborne S chartarum concentration 9.8 _ 5.5
   - one sample collected months after the others was significantly different than the others suggesting difference in sampling technique, lab technique, or environmental conditions; excluding sample 9.8 _ 1.9
   - unnecessarily matched cases and controls on age 9.8 _ 1.5
   
2. Sampling was not uniformly conducted.
   - one investigator collected twice the number of air samples from case homes as from control homes.
   - the methods used to generate artificial aerosols were not uniform ( e.g. vacuuming carpets, pounding on furnace ducts and furniture)
   
3. Water damage could be a confounder.
   - 4 of 8 case homes with water damage were found to contain airborne S chartarum and 3 of 7 control homes with water damage were found to contain airborne S chartarum.
   - little evidence of difference in the presence of airborne S chartarum between water-damaged case and control homes.
   

In addition to study limitations there is limited supportive evidence for the association of S chartarum and pulmonary hemorrhage/hemosiderosis.

• not consistent with historic evidence of illness caused by S chartarum
• association was not observed in Chicago cluster of pulmonary hemorrhage/hemosiderosis cases
  (More information available at: http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00035814.htm:
  Current Trends Acute Pulmonary Hemorrhage Among Infants -- Chicago, April 1992- November 1994 February 03, 1995 / 44(04);67,73-74)
• illness is not observed in flood-prone areas where higher moisture contents may favor growth of S chartarun. (More information available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4909a3.htm: CDC. Update: Pulmonary Hemorrhage/Hemosiderosis Among Infants—Cleveland, Ohio, 1993-1996. MMWR. 2000;49:180-4.)
  
  The association between molds such as S chartarum and acute pulmonary hemorrhage/hemosiderosis in infants was not proven in this study, but that does not mean that there is no association. Further study is needed to determine the cause of the disease. In an effort to standardize the continued research and surveillance for acute pulmonary hemorrhage/hemosiderosis in infants the CDC has established procedures. The first of these procedures to be reported is a recommended clinical description and case definition. (More information available at:http://www.cdc.gov/mmwr/preview/mwrhtml/mm5023a5.htm: CDC. Availability of Case Definition for Acute Idiopathic Pulmonary Hemorrhage in Infants. MMWR. 2001;50:494-5.)

Odds Ratio

Acute pulmonary hemorrhage

Additional Studies

1. Vesper, SJ, Dearborn, DG, Yike, I, Sorenson, WG, and RA Haugland. Hemolysis, Toxicity, and Randomly Amplified Polymorphic DNA Analysis of Stachybotrys chartarum Strains. Applied and Environmental Microbiology 1999(65): 3175- 3181.
   
   Goal:
   “. . . to determine if the strains of S. chartarum isolated from homes in Cleveland where infants developed IPH are unique compared to strains from control homes or strains from other diverse geographic locations.”
   
   Experimental Results:
   
   At 37&Mac176;C, 8 of the 28 strains of S. chartarum observed were consistently able to break down or dissolve red blood cells (hemolytic). 5 of these strains were from Cleveland case homes (31% of Cleveland strains) and 3 were from non-Cleveland strains (25% of non-Cleveland strains).
   
   The spores of all 28 strains showed some amount of toxicity.
   
   3 of the case home strains from Cleveland were the only strains of the 28 tested to be both highly toxic and consistently able to break down red blood cells. Authors suggest that “This observation raises the interesting possibility that a combination of hemolysins and toxins may be required to induce the IPH disorder.”
   
   
2. Vesper, SJ, et al. Quantification of Siderophore and Hemolysin from Stachybotrys chartarum Strains, Including a Strain Isolated from the Lung of a Child with Pulmonary Hemorrhage and Hemosiderosis. Applied and Environmental Microbiology 2000(66):2678-2681.
   
   Goal:
   To determine how the Houston strain of S. chartarum, isolated from the lung of a child with pulmonary hemorrhage/hemosiderosis, compares to strains from the Cleveland case-control study.
   
   Experimental Results:
   The Houston strain and three of the Cleveland case strains showed a 91% relatedness, no significant relationship was found between the Houston strain and any of the control strains.
   The Houston strain was found to be similar to the case strains in production of iron-binding molecules called siderophores, but significantly different from the control house strains (P = 0.009).
   Together, the Houston strain and the Cleveland case produced significantly more (P = <0.001) hemolytic activity than the five control strains. Note*** One of the Cleveland control strains had similar hemolytic activity as that of the Houston and case strains.
   Authors suggest that “It may be that the presence of a case house type strain of S. chartarum in a home is only one factor required for PH expression in an infant.”
   

Limitations of Linking Mold and Disease

1. Molds are present everywhere in the environment.
   
   An individual can be exposed to a mixture of molds on a daily basis making it hard to determine which mold, if any, is causing the symptoms or disease.
   
2. Molds are not always making mycotoxins or releasing spores.
   
   The mere presence of mold indoors does not necessarily mean that there are mycotoxins or spores in the air. Mycotoxins are a secondary metabolite of only certain types of mold. (A secondary metabolite is a product produced by an organism that is not necessary to sustain its life). This means that certain types of mold do not produce mycotoxins at all and those that do, mainly produce mycotoxins when there are unfavorable environmental conditions such as low moisture or nutrient deficiency.
   
   
3. Some of the effects that have been associated with mold exposure are nonspecific.
   
   Syptoms such as coughing, congestion, sneezing, runny nose, eye irritation, sore throat, headaches, excessive fatigue, diarrhea, and dermatitis can be brought on by a number of different exposures.
   
   
4. No proven method to measure mold exposure.
   
   There is currently no proven method to measure the type or amount of mold that a person is exposed to.
   
5. Current methods for measuring indoor molds are not full proof.
   
   Measuring indoor mold concentrations and detecting the species present are difficult for a number of reasons such as the fact that different molds favor different methods of sampling and analysis and molds have periods of inactivity when mold products will not be found in the air.
   
   
6. Two types of the same mold species that produce different mycotoxins can coexist.
   
   It is possible that a single mold species contaminating an indoor environment can be producing more than one type of mycotoxin. Such is the case with Stachybotrys chartarum which can be producing both the highly cytotoxic macrocyclic trichothecenes and the relatively less cytotoxic atranones simultaneously.

Satratoxin H		Atranone

1. There is a lack of scientific data involving the inhalation of molds.
   
   Experiments have been performed providing data on the ingestion of molds and the subsequent health outcomes, but few inhalation studies have been conducted. The defense mechanisms employed by the gastrointestinal sysem differ from that of the respiratory system preventing a direct comparison of ingestion effects to inhalation effects.
   
   
2. Observed individual responses to mold vary.
   
   A response to mold exposure depends on the age, health status, and genetic make-up of an individual. Individuals exposed to the same concentration of indoor mold may display varying symptoms from no observed effect to a severe adverse effect.
   
   
3. The concentration of mold measured in an environment after an individual develops symptoms may not directly reflect the concentration of mold that the individual was exposed to.
   
   Mold is a biological contaminant. The activity of a mold varies on a day-to-day basis, so at any given time the amount of mVOCs, toxins, or spores being released by the mold is dependent on a number of factors including: age of the culture, moisture levels, nutrient availability, stage of reproduction, or presence of a competing organism.
   
   
   

References:

Air Respiratory Health Branch, National Center for Environmental Health, Centers for Disease Control and Prevention. Mold. Available at http://www.cdc.gov/nceh/airpollution/mold/. Viewed on November 14, 2002.
Ammann, HM. Is Indoor Mold Contamination a Threat to Health? Washington State Department of Health. Available at www.doh.wa.gov/ehp/oehas/mold.html. Viewed on November 14, 2002.
CDC. Acute Pulmonary Hemorrhage/Hemosiderosis Among Infant--Cleveland, January 1993 – November 1994. MMWR. 1994;43:881-3. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00033843.htm. Viewed on November 22, 2002.
CDC. Current Trends Acute Pulmonary Hemorrhage Among Infants -- Chicago, April 1992-November 1994. MMWR. 1995;44:67,73-74. Available at http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00035814.htm. Viewed on November 22, 2002.
CDC. Update: Pulmonary Hemorrhage/Hemosiderosis Among Infants—Cleveland, Ohio, 1993-1996. MMWR. 1997;46:33-5. Available at http://www.cdc/gov/mmwr/preview/mmwrhtml/00045680.htm. Viewed on November 22, 2002.
CDC. Update: Pulmonary Hemorrhage/Hemosiderosis Among Infants—Cleveland, Ohio, 1993-1996. MMWR. 2000;49:180-4. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4909a3.htm. Viewed on November 22, 2002.
CDC. Availability of Case Definition for Acute Idiopathic Pulmonary Hemorrhage in Infants. MMWR. 2001;50:494-5. Available at http://www.cdc.gov/mmwr/preview/mwrhtml/mm5023a5.htm. Viewed on November 22, 2002.
Jarvis, BB. Chemistry and toxicology of molds isolated from water-damaged buildings. Advances in Experimental Medicine and Biology 2002(504): 43-52.
Nelson, BD. Stachybotrys chartarum: The Toxic Indoor Mold. American Phytopathological Society. Available at http://www.aspnet.org. Viewed on December 6, 2002.
Vesper, SJ, Dearborn, DG, Yike, I, Sorenson, WG, and RA Haugland. Hemolysis, Toxicity, and Randomly Amplified Polymorphic DNA Analysis of Stachybotrys chartarum Strains. Applied and Environmental Microbiology 1999(65): 3175- 3181.
Vesper, SJ, et al. Quantification of Siderophore and Hemolysin from Stachybotrys chartarum Strains, Including a Strain Isolated from the Lung of a Child with Pulmonary Hemorrhage and Hemosiderosis. Applied and Environmental Microbiology 2000(66):2678-2681.