3 New studies of Pulmnary & Water Damaged Buildings, NIOSH, JOEM, JTox

August 13, 2006

Hi All,

Below are three news studies on the subject of illness caused by damp indoor buildings.

1.Health Effects Laboratory Division, National Institute for Occupational Safety and Health, town, West Virginia 26505, USA. sby5@...

: Inhal Toxicol. 2006 Oct;18(11):865-74.Pulmonary exposure to 1 --> 3-beta-glucan alters adaptive immune responses in rats.

Young SH,

JR,

Antonini JM.

1 --> 3-beta-glucans have been associated with increased pulmonary inflammation in fungal-related indoor air problems. Epidemiological studies have shown a correlation between increases in T-cell proliferation and decreases in CD4+/CD8+ ratio after exposure to fungi. The objective of the present investigation was to determine the mechanisms by which 1 --> 3-beta-glucans affect immune responses using an animal model. Rats received a single dose of zymosan A (2.5 mg/kg body weight) via intratracheal instillation (IT) and were euthanized on days 1, 4, 6, 8, and 10 post IT. Bronchoalveolar lavage was performed at each time point post-IT. Inflammation and lung injury were assessed by measuring neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and by measuring albumin and lactate dehydrogenase levels in BALF, respectively. Alveolar macrophage activation was determined by chemiluminescence. Immune response was characterized via immunophenotyping of bronchoalveolar lavage cells and lymphocytes isolated from the lung-associated lymph nodes. Upon challenge with zymosan, rats exhibited increased inflammation and injury at early time points (days 1 and 4) post IT exposure. Although elevations in neutrophil infiltration and chemiluminescence had returned to control levels on day 4, lymphocytes recovered from lung-associated lymph nodes continued to proliferate and reached a maximum on day 6. The CD4+/CD8+ T cell ratio from lymph nodes was lower in zymosan-treated rats than in control rats. Zymosan treatment increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and IL-12p70 secretion in BALF on day 1. In summary, rats exposed to zymosan had an increase in acute inflammation, and the altered lymphocyte profiles were consistent with the findings of epidemiology studies.

PMID: 16864404 [PubMed - indexed for MEDLINE]

2. J Occ Environ Med. 2006 Aug;48(8):852-858.

Specific Molds Associated With Asthma in Water-Damaged Homes.Vesper SJ, McKinstry C, Yang C, Haugland RA, Kercsmar CM, Yike I, Schluchter MD, Kirchner HL, Sobolewski J, Allan TM, Dearborn DG.From the U.S. Environmental Protection Agency (Dr Vesper, Dr Haugland), Cincinnati, Ohio; Pacific Northwest National Laboratory (Dr McKinstry), Richland, Washington; P & K Microbiology Services (Dr Yang), Cherry Hill, New Jersey; Department of Pediatrics (Dr Kercsmar, Dr Yike, Dr Schluchter, Dr Kirchner, Dr Dearborn), Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio; and Cuyahoga County Board of Health (Mr Sobolewski, Mr Allan), Cleveland, Ohio.OBJECTIVE:: We sought to determine if specific molds were found in significantly higher concentrations in the water-damaged homes of asthmatic children compared with homes with no visible water damage. METHODS:: The mold concentrations in the dust in asthmatic children's bedrooms in water-damaged homes (N = 60) and control homes (N = 22) were measured by mold-specific quantitative polymerase chain reaction. RESULTS:: Two molds, Scopulariopsis brevicaulis and Trichoderma viride, had significantly (P < 0.05) higher concentrations in asthmatics' homes compared with control homes and three other molds (Penicillium crustosum group, Stachybotrys chartarum, and Wallemia sebi) had P values <0.1. CONCLUSIONS:: A relative moldiness index was developed to predict the likely development of asthma in water-damaged homes in Cleveland.PMID: 16902378 [PubMed - as supplied by publisher]

3. Comparison of Inflammatory Responses in Mouse Lungs Exposed to Atranones A And C from Stachybotrys Chartarum

G. Rand A1, J. Flemming A1, J. A2, Taiwo O. Womiloju A2

A1 Department of Biology, Saint 's University, Halifax, Nova Scotia, CanadaA2 Department of Chemistry, Carleton University, Ottawal, Ontario, Canada

Abstract:

Stachybotrys chartarum isolates can be separated into two distinct chemotypes based on the toxins they produce. One chemotype produces macrocyclic trichothecenes; the other produces atranones (and sometimes simple trichothecenes, e.g., trichodermol and trichodermin). Studies using in vivo models of lung disease revealed that exposure to spores of the atranone producing S. chartarum isolates led to a variety of immunotoxic, inflammatory, and other pathological changes. However, it is unclear from these studies what role the pure atranone toxins sequestered in spores of these isolates exert on lung disease onset. This study examined dose-response (0.2, 1.0, 2.0, 5.0, or 20 Î¼g atranone/animal) and time-course (3, 6, 24, and 48 h postinstillation [PI]) relationships associated with inflammatory cell and proinflammatory chemokine/cytokine responses in mouse lungs intratracheally instilled with two pure atranones (either A or C) isolated from S. chartarum. High doses (2.0 to 20 Î¼g toxin/animal) of atranone A and C induced significant inflammatory responses manifested as differentially elevated macrophage, neutrophil, macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations in the bronchioalveolar lavage fluid (BALF) of intratracheally exposed mice. Compared to controls, BALF macrophage and neutrophil numbers were increased to significant levels from 6 to 48 h (PI). Except for macrophage numbers in atranone A treatment animals, cells exhibited significant dose dependent-like responses. The chemokine/cytokine marker responses were significantly and dose-dependently increased from 3 to 24 h PI and declined to nonsignificant levels at 48 h PI. The results suggest not only that atranones are inflammatory but also that they exhibit different inflammatory potency with different toxicokinetics. Data also suggest that exposure to these toxins in spores of S. chartarum in contaminated building environments could contribute to inflammatory lung disease onset in susceptible individuals.

August 14, 2006

Based on what I read.....

One is a rat study using controlled (not real-world) conditions.

One is a real-world study of water damaged homes in Ohio looking at correlations between molds and asthma. Good stuff!

One is a mouse study using controlled (not real-world) conditions.

Bottom line....two rodent studies versus one real-world study. Take them for what they are worth.

--

Geyer, PE, CIH, CSP

President

KERNTEC Industries, Inc.

Bakersfield, California

www.kerntecindustries.com

Hi All,

Below are three news studies on the subject of illness caused by damp indoor buildings.

1.Health Effects Laboratory Division, National Institute for Occupational Safety and Health, town, West Virginia 26505, USA. sby5@...

: Inhal Toxicol. <javascript:AL_get(this, 'jour', 'Inhal Toxicol.');> 2006 Oct;18(11):865-74.Pulmonary exposure to 1 --> 3-beta-glucan alters adaptive immune responses in rats.

Young SH <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & amp;cmd=Search & amp;itool=pubmed_AbstractPlus & amp;term=%22Young+SH%22%5BAuthor%5D> ,

JR <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & amp;cmd=Search & amp;itool=pubmed_AbstractPlus & amp;term=%22+JR%22%5BAuthor%5D> ,

Antonini JM <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & amp;cmd=Search & amp;itool=pubmed_AbstractPlus & amp;term=%22Antonini+JM%22%5BAuthor%5D> .

1 --> 3-beta-glucans have been associated with increased pulmonary inflammation in fungal-related indoor air problems. Epidemiological studies have shown a correlation between increases in T-cell proliferation and decreases in CD4+/CD8+ ratio after exposure to fungi. The objective of the present investigation was to determine the mechanisms by which 1 --> 3-beta-glucans affect immune responses using an animal model. Rats received a single dose of zymosan A (2.5 mg/kg body weight) via intratracheal instillation (IT) and were euthanized on days 1, 4, 6, 8, and 10 post IT. Bronchoalveolar lavage was performed at each time point post-IT. Inflammation and lung injury were assessed by measuring neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and by measuring albumin and lactate dehydrogenase levels in BALF, respectively. Alveolar macrophage activation was determined by chemiluminescence. Immune response was characterized via immunophenotyping of bronchoalveolar lavage cells and lymphocytes isolated from the lung-associated lymph nodes. Upon challenge with zymosan, rats exhibited increased inflammation and injury at early time points (days 1 and 4) post IT exposure. Although elevations in neutrophil infiltration and chemiluminescence had returned to control levels on day 4, lymphocytes recovered from lung-associated lymph nodes continued to proliferate and reached a maximum on day 6. The CD4+/CD8+ T cell ratio from lymph nodes was lower in zymosan-treated rats than in control rats. Zymosan treatment increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and IL-12p70 secretion in BALF on day 1. In summary, rats exposed to zymosan had an increase in acute inflammation, and the altered lymphocyte profiles were consistent with the findings of epidemiology studies.

PMID: 16864404 [PubMed - indexed for MEDLINE]

2. J Occ Environ Med. <javascript:AL_get(this, 'jour', 'J Occup Environ Med.');> 2006 Aug;48(8):852-858.

<http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?itool=Abstract-def & amp;PrId=3159 & amp;uid=16902378 & amp;db=PubMed & amp;url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00043764-200608000-00014>

Specific Molds Associated With Asthma in Water-Damaged Homes.

>From the U.S. Environmental Protection Agency (Dr Vesper, Dr Haugland), Cincinnati, Ohio; Pacific Northwest National Laboratory (Dr McKinstry), Richland, Washington; P & K Microbiology Services (Dr Yang), Cherry Hill, New Jersey; Department of Pediatrics (Dr Kercsmar, Dr Yike, Dr Schluchter, Dr Kirchner, Dr Dearborn), Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio; and Cuyahoga County Board of Health (Mr Sobolewski, Mr Allan), Cleveland, Ohio.

OBJECTIVE:: We sought to determine if specific molds were found in significantly higher concentrations in the water-damaged homes of asthmatic children compared with homes with no visible water damage. METHODS:: The mold concentrations in the dust in asthmatic children's bedrooms in water-damaged homes (N = 60) and control homes (N = 22) were measured by mold-specific quantitative polymerase chain reaction. RESULTS:: Two molds, Scopulariopsis brevicaulis and Trichoderma viride, had significantly (P < 0.05) higher concentrations in asthmatics' homes compared with control homes and three other molds (Penicillium crustosum group, Stachybotrys chartarum, and Wallemia sebi) had P values <0.1. CONCLUSIONS:: A relative moldiness index was developed to predict the likely development of asthma in water-damaged homes in Cleveland.

PMID: 16902378 [PubMed - as supplied by publisher]

3. Comparison of Inflammatory Responses in Mouse Lungs Exposed to Atranones A And C from Stachybotrys Chartarum

G. Rand A1, J. Flemming A1, J. A2, Taiwo O. Womiloju A2

A1 Department of Biology, Saint 's University, Halifax, Nova Scotia, Canada

A2 Department of Chemistry, Carleton University, Ottawal, Ontario, Canada

Abstract:

Stachybotrys chartarum isolates can be separated into two distinct chemotypes based on the toxins they produce. One chemotype produces macrocyclic trichothecenes; the other produces atranones (and sometimes simple trichothecenes, e.g., trichodermol and trichodermin). Studies using in vivo models of lung disease revealed that exposure to spores of the atranone producing S. chartarum isolates led to a variety of immunotoxic, inflammatory, and other pathological changes. However, it is unclear from these studies what role the pure atranone toxins sequestered in spores of these isolates exert on lung disease onset. This study examined dose-response (0.2, 1.0, 2.0, 5.0, or 20 ¦Ìg atranone/animal) and time-course (3, 6, 24, and 48 h postinstillation [PI]) relationships associated with inflammatory cell and proinflammatory chemokine/cytokine responses in mouse lungs intratracheally instilled with two pure atranones (either A or C) isolated from S. chartarum. High doses (2.0 to 20 ¦Ìg toxin/animal) of atranone A and C induced significant inflammatory responses manifested as differentially elevated macrophage, neutrophil, macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations in the bronchioalveolar lavage fluid (BALF) of intratracheally exposed mice. Compared to controls, BALF macrophage and neutrophil numbers were increased to significant levels from 6 to 48 h (PI). Except for macrophage numbers in atranone A treatment animals, cells exhibited significant dose dependent-like responses. The chemokine/cytokine marker responses were significantly and dose-dependently increased from 3 to 24 h PI and declined to nonsignificant levels at 48 h PI. The results suggest not only that atranones are inflammatory but also that they exhibit different inflammatory potency with different toxicokinetics. Data also suggest that exposure to these toxins in spores of S. chartarum in contaminated building environments could contribute to inflammatory lung disease onset in susceptible individuals.

August 14, 2006

See Below, noting that I have only read what is below. I may change my mind if get to read all of the studies.

........................................................................... "Tony" Havics, CHMM, CIH, PEpH2, LLCPO Box 34140Indianapolis, IN 46234 cell90% of Risk Management is knowing where to place the decimal point...any consultant can give you the other 10%â„ This message is from pH2. This message and any attachments may contain legally privileged or confidential information, and are intended only for the individual or entity identified above as the addressee. If you are not the addressee, or if this message has been addressed to you in error, you are not authorized to read, copy, or distribute this message and any attachments, and we ask that you please delete this message and attachments (including all copies) and notify the sender by return e-mail or by phone at . Delivery of this message and any attachments to any person other than the intended recipient(s) is not intended in any way to waive confidentiality or a privilege. All personal messages express views only of the sender, which are not to be attributed to pH2 and may not be copied or distributed without this statement.

-----Original Message-----From: iequality [mailto:iequality ] On Behalf Of snk1955@...Sent: Monday, August 14, 2006 12:06 AMTo: sickbuildings Cc: iequality ; AspergillusSupport@...Subject: 3 New studies of Pulmnary & Water Damaged Buildings, NIOSH, JOEM, JTox

Hi All,

Below are three news studies on the subject of illness caused by damp indoor buildings.

1.Health Effects Laboratory Division, National Institute for Occupational Safety and Health, town, West Virginia 26505, USA. sby5@...

: Inhal Toxicol. 2006 Oct;18(11):865-74.Pulmonary exposure to 1 --> 3-beta-glucan alters adaptive immune responses in rats.

Young SH,

JR,

Antonini JM.

1 --> 3-beta-glucans have been associated with increased pulmonary inflammation in fungal-related indoor air problems. Epidemiological studies have shown a correlation between increases in T-cell proliferation and decreases in CD4+/CD8+ ratio after exposure to fungi. The objective of the present investigation was to determine the mechanisms by which 1 --> 3-beta-glucans affect immune responses using an animal model. Rats received a single dose of zymosan A (2.5 mg/kg body weight) via intratracheal instillation (IT) and were euthanized on days 1, 4, 6, 8, and 10 post IT. Bronchoalveolar lavage was performed at each time point post-IT. Inflammation and lung injury were assessed by measuring neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and by measuring albumin and lactate dehydrogenase levels in BALF, respectively. Alveolar macrophage activation was determined by chemiluminescence. Immune response was characterized via immunophenotyping of bronchoalveolar lavage cells and lymphocytes isolated from the lung-associated lymph nodes. Upon challenge with zymosan, rats exhibited increased inflammation and injury at early time points (days 1 and 4) post IT exposure. Although elevations in neutrophil infiltration and chemiluminescence had returned to control levels on day 4, lymphocytes recovered from lung-associated lymph nodes continued to proliferate and reached a maximum on day 6. The CD4+/CD8+ T cell ratio from lymph nodes was lower in zymosan-treated rats than in control rats. Zymosan treatment increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and IL-12p70 secretion in BALF on day 1. In summary, rats exposed to zymosan had an increase in acute inflammation, and the altered lymphocyte profiles were consistent with the findings of epidemiology studies.

Not surprising - only confirms studies in humans but without apparent dose data here. So what is trhe correlation to humans? do they state it??

PMID: 16864404 [PubMed - indexed for MEDLINE]

2. J Occ Environ Med. 2006 Aug;48(8):852-858.

Specific Molds Associated With Asthma in Water-Damaged Homes.Vesper SJ, McKinstry C, Yang C, Haugland RA, Kercsmar CM, Yike I, Schluchter MD, Kirchner HL, Sobolewski J, Allan TM, Dearborn DG.From the U.S. Environmental Protection Agency (Dr Vesper, Dr Haugland), Cincinnati, Ohio; Pacific Northwest National Laboratory (Dr McKinstry), Richland, Washington; P & K Microbiology Services (Dr Yang), Cherry Hill, New Jersey; Department of Pediatrics (Dr Kercsmar, Dr Yike, Dr Schluchter, Dr Kirchner, Dr Dearborn), Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio; and Cuyahoga County Board of Health (Mr Sobolewski, Mr Allan), Cleveland, Ohio.OBJECTIVE:: We sought to determine if specific molds were found in significantly higher concentrations in the water-damaged homes of asthmatic children compared with homes with no visible water damage. METHODS:: The mold concentrations in the dust in asthmatic children's bedrooms in water-damaged homes (N = 60) and control homes (N = 22) were measured by mold-specific quantitative polymerase chain reaction. RESULTS:: Two molds, Scopulariopsis brevicaulis and Trichoderma viride, had significantly (P < 0.05) higher concentrations in asthmatics' homes compared with control homes and three other molds (Penicillium crustosum group, Stachybotrys chartarum, and Wallemia sebi) had P values <0.1. CONCLUSIONS:: A relative moldiness index was developed to predict the likely development of asthma in water-damaged homes in Cleveland.

Bad conclusion: "likely development of asthma" . Unless there is more to it (e.g., longitudinally based study with comparable pre and post exposdure data) , then the conclusion is an association not "development" or "causation". I would expect the result preented - but it still is a wrong conclusion in the manner presented.

PMID: 16902378 [PubMed - as supplied by publisher]

3. Comparison of Inflammatory Responses in Mouse Lungs Exposed to Atranones A And C from Stachybotrys Chartarum

G. Rand A1, J. Flemming A1, J. A2, Taiwo O. Womiloju A2

A1 Department of Biology, Saint 's University, Halifax, Nova Scotia, CanadaA2 Department of Chemistry, Carleton University, Ottawal, Ontario, Canada

Abstract:

Stachybotrys chartarum isolates can be separated into two distinct chemotypes based on the toxins they produce. One chemotype produces macrocyclic trichothecenes; the other produces atranones (and sometimes simple trichothecenes, e.g., trichodermol and trichodermin). Studies using in vivo models of lung disease revealed that exposure to spores of the atranone producing S. chartarum isolates led to a variety of immunotoxic, inflammatory, and other pathological changes. However, it is unclear from these studies what role the pure atranone toxins sequestered in spores of these isolates exert on lung disease onset. This study examined dose-response (0.2, 1.0, 2.0, 5.0, or 20 Î¼g atranone/animal) and time-course (3, 6, 24, and 48 h postinstillation [PI]) relationships associated with inflammatory cell and proinflammatory chemokine/cytokine responses in mouse lungs intratracheally instilled with two pure atranones (either A or C) isolated from S. chartarum. High doses (2.0 to 20 Î¼g toxin/animal) of atranone A and C induced significant inflammatory responses manifested as differentially elevated macrophage, neutrophil, macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations in the bronchioalveolar lavage fluid (BALF) of intratracheally exposed mice. Compared to controls, BALF macrophage and neutrophil numbers were increased to significant levels from 6 to 48 h (PI). Except for macrophage numbers in atranone A treatment animals, cells exhibited significant dose dependent-like responses. The chemokine/cytokine marker responses were significantly and dose-dependently increased from 3 to 24 h PI and declined to nonsignificant levels at 48 h PI. The results suggest not only that atranones are inflammatory but also that they exhibit different inflammatory potency with different toxicokinetics. Data also suggest that exposure to these toxins in spores of S. chartarum in contaminated building environments could contribute to inflammatory lung disease onset in susceptible individuals.Note terms: "susceptible individuals" and "toxins in spores" and "inflammatory lung disease". Susceptible is a little vague. For Toxins in spores - What are the levels used in this study compared to that present in the real world, are they always produced, are intratracheally injected in the real world, etc. For inflammatory kung disease - what is it there are saying - end result irritation, or asthma or increased risk of infection or what? Classical study to state that they need more money to support another study.

August 17, 2006

Hi Tony, all:

based on my reading of this material for more than a decade, I tend to assign a higher value to articles authored by certain persons, some of whom appear in these papers.

in the three articles Sharon presented, I find familiar names of researchers, clinicians, and practitioners whom I've learned to respect and trust. these names include J , Chin Yang, Steve Vesper and Dorr Dearborn (there are many others).

we don't have a sufficient number of the right type of research efforts to fully address the question of biological plausibility, let alone quantify the risks. of course we don't. if these were easy questions, we'd already have the answers we so desperately seek.

as usual, solid research proceeds at a snail's pace, and there's never enough funding to rigorously apply the scientific method to every piece of the puzzle, every step in linking presence to exposure, and thence to human response. I've found that the real trick is studying (and comprehending!) the published materials from a variety of sources, and synthesizing an understanding that is based on the science (with all its warts).

if folks on this list are looking for definitive answers to the questions raised by the IOM and others -- take note: they're just not out there. at least not yet. the sense I've gotten of late is that we're making good progress, but a reasonable degree of certainty in the answers remains beyond our reach. fear mongers and mold minimizers alike remain on shaky ground.

Wane

<><><><><><><><><><><> Wane A. Baker, P.E., CIH Division Manager, Indoor Air Quality MICHAELS ENGINEERING"Real Professionals. Real Solutions"

La Crosse, Twin Cities, Milwaukee

Phone , ext. 484 Cell Fax

mailto:wab@... On the web at: http://www.michaelsengineering.com

"To love what you do and feel that it matters - how could anything be more fun?" - Graham

>> See Below, noting that I have only read what is below. I may change my mind if get to read all of the studies.> > > ..........................................................................> "Tony" Havics, CHMM, CIH, PE> pH2, LLC> > 3 New studies of Pulmnary & Water Damaged Buildings, NIOSH, JOEM, JTox> > > > Hi All,> > Below are three news studies on the subject of illness caused by damp indoor buildings.>

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