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??