The Health Effects of Mold in Children

The Health Effects of Mold in
Children
James M. Seltzer, M.D.
Clinical Professor of Medicine
Co-Director
Pediatric Environmental Health Specialty Unit
US EPA Region IX
University of California, Irvine
School of Medicine
Mold




What is it?
Where is it?
Mechanisms of Illness
Relationship to hypersensitivity?
What Is Mold?
Mold and mildew are members of the fungi kingdom which feed on
organic material and are critical decomposition agents of plant
and animal debris.
Micro-fungi (mold)
Mushrooms
Dryrot fungi
REQUIREMENTS FOR MOLD
GROWTH
• Sufficient moisture
• Cellulose or organic food source
• Spores present on surface
• Suitable temperature
Window Colonizing Molds
In a vast majority of cases, Cladosporium species are the
most common colonizers of windows and walls (condensation).
Growth appears olive
green to dark brown
Carpet & Carpet Tack Colonizing
Molds
Penicillium / Aspergillus
Cladosporium
Alternaria
Arthrinium
Chaetomium
Torula
Wall Cavity Molds
Stachybotrys
Alternaria
Pithomyces
Mechanisms of Disease

Hypersensitivity
Immunologic
 Non-immunologic




Infectious
Toxic
(Irritant)
Hypersensitivity
Types (mechanism defined)
Immunologic
 Non-immunologic

Diagnosis of mold
hypersensitivity



History of exposure
Clinical picture of known moldrelated hypersensitivity disorders
Laboratory findings
Diagnosis of mold
hypersensitivity

History of exposure
Route
 Concentration
 Duration

Diagnosis of mold
hypersensitivity

Clinical picture of known moldrelated hypersensitivity disorders
Allergic rhinitis
 Asthma
 Allergic bronchopulmonary
mycosis
 Allergic fungal sinusitis

Allergic Fungal Sinusitis
Making the Diagnosis
•
•
•
•
•
•
•
Poor response to antibiotics
Elevated total serum IgE
Elevated specific IgE
Elevated specific IgG
Imaging – CT of sinuses
No fungal invasion of tissue
Typical pathology
Diagnosis of mold
hypersensitivity

Clinical picture of known moldrelated hypersensitivity disorders
Anaphylaxis
 Urticaria, eczema?
 Hypersensitivity pneumonitis
 Organic Dust Toxic Syndrome
(ODTS), humidifier fever

Mold: Fact & Fantasy
Health Disorders

Unproven disorders
Mold/food hypersensitivity without
specific IgE
 Toxic encephalopathy
 Mycotoxicosis
 Toxic mold
 Systemic Candidiasis
 Lyme disease
 Autism/PDD

Diagnosis of mold
hypersensitivity

Laboratory findings

Assays for serum specific IgE
Skin testing – prick and intradermal
 In vitro – RAST, Immunocap
(ELISA)

Total serum IgE
 CBC with differential
 IgG precipitins (agar double
diffusion)
 Lung Function Testing

Vulnerable Populations

Immunosuppressed
Cancer
 Chemotherapy
 Transplant
 Very young and very old (?)
 Immunodeficiency
 Conditions with associated
immune dysfunction


Previously sensitized
(immunologically)
Housing characteristics, reported mold
exposure, and asthma in the European
Community Respiratory Health Survey
Associations between current housing characteristics
and asthma outcomes (meta-analyses)
•Wheezing in past year, Wheezing apart from colds in past
year, Current Asthma, Bronchial Responsiveness
Prevalence Odds Ratios
•Ducted air heating 1.07, 1.16,1.43, 1.02
•Air Conditioning 1.31, 1.01, 1.46, 1.05
•Water Damage in last year 1.16, 1.23, 1.13, 1.15
•Water on basement floors 1.46, 1.26, 1.54, 1.05
•Mold or mildew in past year 1.34, 1.44, 1.28, 1.14
Jan-Paul Zock, PhD,a Deborah Jarvis, MD,b Christina Luczynska, PhD,b Jordi Sunyer, MD,a
and Peter Burney, MD,b on behalf of the European Community Respiratory Health Survey*
Barcelona, Spain, and London, United Kingdom J Allergy Clin Immunol 2002;110:285-92
Meta-Analyses of Associations of
Respiratory Health Effects with
Dampness and Mold in Homes
Fisk, WJ, et al., Indoor Air 2007; in
press


Only studies (n-33) with reports (either
researcher or occupants) of visible
dampness and/or mold or mold odor
Health outcomes







Upper respiratory tract symptoms
Cough
Wheeze
Asthma diagnosis
Current asthma
Asthma development
“Building dampness & mold are associated
with approx. 30-50% increases in
respiratory and asthma-related health
outcomes”
James M Seltzer, MD
20
Public health and economic
impact of dampness and mold,
Mudarri, D and Fisk, WJ, Indoor
Air 2007; 17:226



Proportion of asthma cases attributable
to dampness and mold exposure = 21%
(based upon data from Fisk’s metaanalysis)
Literature of mold/dampness in schools,
offices, and institutional buildings =
similar attributable risk as homes
Applying attributable fraction of national
annual cost of asthma → approx. $3.5
billion ($2.1 - $4.8 billion) in homes
James M Seltzer, MD
21
What are “typical” mold spore levels?
Range, Median, & 1 standard deviation based on slit impaction sampling methods
1,000,000
Range (low – high measurement)
Total spores (median -> 1 std. dev.)
Aspergillus / Penicillium (median -> 1 std. dev.)
100,000
10,000
1,000
100
Outdoors
Clean
Residential
Water-stained
residential
Mold
Growth
IOM’s 2004 Conclusions
Summary
Health Outcomes and Exposure to
Damp Indoor Environments

Sufficient Evidence of Causal
Relationship


No outcomes
Sufficient Evidence of Association
Upper respiratory tract symptoms
 Cough
 Wheeze
 Asthma symptoms in sensitized
asthmatics

IOM’s 2004 Conclusions
Summary
Health Outcomes and Exposure to
Damp Indoor Environments

Limited or Suggestive Evidence of an
Association
Shortness of breath
 Lower respiratory tract illnesses in
otherwise healthy children
 Asthma development

IOM’s 2004 Conclusions
Summary
Health Outcomes and Presence of
Mold or Other Agents in Damp
Indoor Environments

Sufficient Evidence of a Causal
Relationship

No outcomes
IOM’s 2004 Conclusions
Summary
Health Outcomes and Presence of Mold
or Other Agents in Damp Indoor
Environments

Sufficient Evidence of Association
 URT symptoms (nose & throat)
 Wheeze
 Cough
 Asthma sxs in sensitized asthmatic persons
 Hypersensitivity pneumonitis in
susceptible persons (mold & bacteria)
IOM’s 2004 Conclusions
Summary
Health Outcomes and Presence of
Mold and Other Agents in Damp
Indoor Environments

Limited or Suggestive Evidence of
an Association

Lower respiratory tract illness in
otherwise healthy children
What do we need to know?



Accurate measurements of fungal
components
The environmental and clinical significance
of these data
Dose-response relationships between fungal
contaminant and human subject




Sensitive individuals
Non-sensitive individuals
Synergy of clinical effects for fungal
contaminants
Results of appropriately designed valid
scientific studies evaluating alleged
unproven adverse health outcomes and
mold associations
What do we need?

CUTE SUBJECTS with the putative
disorders
What do we need?

KNOWLEDGEABLE SCIENTISTS with well
designed studies asking the right questions
What do we need?

MONEY to FUND the studies
Recent References

Institute of Medicine, Clearing the Air - Asthma
and Indoor Air Exposures, The National
Academies Press, Washington, D.C., 2000.

Institute of Medicine, Damp Indoor Spaces
and Health, The National Academies Press,
Washington, D.C., 2004.

Storey, E., Dangman, K.H., et al., Guidance
for Clinicians on the Recognition and
Management of Health Effects Related to Mold
Exposure and Moisture Indoors, University of
Connecticut Health Center, Division of
Occupational and Environmental Health, 2004.
Recent References

Trout, D.B., Seltzer, J.M., et al., “Clinical Use
of Immunoassays in Assessing Exposure to
Fungi and Potential Health Effects Related to
Fungal Exposure”, Ann. Allergy Asthma
Immunol. 92:483, 2004.

Hirvonen, M.R., Huttunen, K., Roponen, M.,
“Bacterial strains from moldy buildings are
highly potent inducers of inflammatory and
cytotoxic effects”, Indoor Air Suppl 9:65,
2005.

Laumbach, R.J. and Kipen, H.M.,
“Bioaerosols and sick building syndrome:
particles, inflammation, and allergy”, Cur.
Opin. Allergy Clin. Immunol. 5:135, 2005.
Recent References

Kuhn, D.M. and Ghannoum, M.A., “Indoor mold,
toxigenic fungi, and Stachybotrys chartarum:
infectious disease perspective”, Clin. Microbiol.
Rev. 16:144, 2003.

Baxter, D & Seltzer, JM, “A Regional Comparison
of Mold Spore Concentrations Outdoors and
Inside “Clean” and “Mold Contaminated” Southern
California Buildings”, Journal of Occupational and
Environmental Hygiene, 2:8-18, 2005.

Seltzer, J.M. and Fedoruk, M.J., “Health effects of
mold in children”, Pediatr. Clin. North Am.
54(2):309, 2007.

www.indoorhygienictechnologies.com
MOLD RESOURCES
http://www.acaai.org
http://www.epa.gov/iaq/molds/moldresourc
es.html
http://www.aaaai.org/nab/index.cfm?p=faq
Scientific Perspective





Methodology Problems
Unproven Theories
Unproven Therapies
Causation determination
Good practices
Methodology problems:
Many publications alleging various
symptoms and diseases caused by
exposure in moldy environments provide
 Inadequate documentation of
exposure or data (e. g. P.E. done
but results not stated
 Inadequate data collected, e. g.,
• Non-validated questionnaires or self
report from evaluators or subjects
• Lack of physical examinations and
expert diagnosis
• No quantification of mold exposure –
surface, air
Scientific Perspective
Methodology problems
 Lack of scientifically valid
specific disease or objective
findings
Scientific Perspective
Methodology problems

Misinterpretation of significance of
data or findings
Mold spore concentrations in air
 Relevance or sufficiency of data to
make diagnosis, e.g., PFTs
 Use of non-validated tests, e.g.,
Antibodies against mycotoxins or
non-IgE antibodies to molds

Scientific Perspective
Unproven Theories


Use of specific IgG to diagnose mold
hypersensitivity
Use of serum levels of any class of
antibody to determine
Exposure characteristics relating
to a specific mold
 Exposure characteristics relating
to any mycotoxin
 Illness relating to any mycotoxins
 effectiveness of therapy

Scientific Perspective
Unproven therapies
 Mold-elimination diet
 Anti-fungal agents, e.g.,
Sporanox, Nizoral (including
intra-nasal)
Scientific Perspective
Causation determination
 Scientific
 Clinical
 Legal
Scientific Perspective
Good practices
 Thorough history
 Relevant P. E.
 Review of prior medical records
where appropriate
 Relevant appropriate laboratory
testing
 Relevant appropriate imaging
studies
Scientific Perspective
Good Practices
 Establish degree of exposure
if possible
 Diagnosis should consider
valid science, established
diagnosis that can be caused
by mold, and good fit with the
data
 If in litigation, consider
differences between scientific
proof of causation and the
legal standard of causation.
Erroneous Assumptions


Presence of toxigenic mold =
presence of mycotoxins
Presence of molds in indoor
environment




= exposure
= causation of disease
Presence of health disorder or sxs
that can be caused by mold =
causation by molds
Sxs follow exposure = causation
Determining Causation

Grounded in the principals of
appropriate medical evaluation
Medical history
 Physical examination
 Laboratory evaluation
 Differential Dx
 Final Dx

Determining Causation

Medical Hx
Patient self-report form
 Face-to-face inquiry with critical listening
 Review all relevant medical records (at
least 5-10 years preceding injury) –
particularly important for forensic medicine
 Critically review environmental information
and reports

Determining Causation

Physical examination – focused and
relevant


Differential Dx – consider all reasonable
possibilities, including non-mold
etiologies
Laboratory/Imaging, e.g.,
Allergy skin testing
 Lung function testing
 Blood testing
 Sinus & chest x-rays, CT scans



Referral (if needed)
Determine Causation
Establishing Causation

To establish causation






Injury must be c/w known pathophysiologic mechanism for
specific mold-induced injury
Adequate mold exposure known to cause the specific injury
must be established
Temporal relationship is consistent
Other reasonably possible causes must be excluded
Laboratory and imaging findings are c/w Dx
Ideally, expected response to appropriate treatment for the
disorder
Allergic Fungal Sinusitis
Effective Treatment
•
•
•
•
•
Systemic corticosteroids
Systemic anti-fungal antibiotics
Topical anti-fungal antibiotics
May require surgery
Allergy immunotherapy??