Goals and Objectives

• To discuss illnesses caused or exacerbated by mold exposure

• To discuss the impact of hurricane Katrina related flood damage and resulting mold exposure on human health

• To briefly describe mold remedial measures and mold associated medico-legal issues

Case #1Case #1

• PC is a 65 y/o male with a hx of allergic rhinitis chronic cough( post nasal drip) who has a 10 year history of allergen IT with his symptoms being totally controlled with Dust mite immunotherapy on maintenance. He denied wheezing SOB,

Skin Prick test result comparison Skin Prick test result comparison

Pre Katrina 1998 Post Katrina 2006

Grasses Neg. Pos. (Italian rye)

Trees Neg. Pos.

Dust mite Pos. Pos.

Weeds Neg. Neg.

Molds

Penicillium

Neg. Pos.

Aspergillus Neg. Pos.

Cladosporium Neg. Pos.

HPIHPI

• Post Katrina with a 8 month hiatus in immunotherapy he had a total of 5 ER visits , wheezing , SOB, exacerbation of rhinitis symptoms , several antibiotic courses for sinusitis and systemic oral steroids for asthma exacerbations

• He was also found to have AERD (Aspirin exacerbated respiratory disease) demonstrated by history latter confirmed by challenge.

CONT of HPICONT of HPI

• Skin prick tests prior to Katrina were only positive to dust mite.

• Pmhx: Allergic rhinitis, chronic cough, chronic sinusitis and allergen immunotherapy

• PShx: Sinus Surgery 2000 for nasal polyps• Meds: Amoxicillin, Guafinessin, desloratidine,

fluticosone, albuterol and budesonide nasal spray

• Drug Allergies: Aspirin hypersensitivity

Physical ExamPhysical Exam

• Vital signs: 180lbs, temp 98.3, Bp 138/74

• Nares congested

• Lungs clear

• Rest of exam within normal limits

Assesment/ PlanAssesment/ Plan

• Exacerbation of Allergic rhinitis, sinusitis, chronic cough with possible GERD association

• Chest x ray wnl• Amoxicillin/Clavulinic acid 875 mg po bid for

suspected sinusitis• desloratidine Qam• Azelastine spray each nostril qd• Fluticasone inhaler Bid • PEFR twice daily• Albuterol prn

Common Allergenic MoldsCommon Allergenic Molds

Position PaperPosition Paper

• The medical effects of Mold Exposure (Bush Retal: JACI 2006; 117: 326-333)

Mechanism of Fungal DiseaseMechanism of Fungal Disease

1- Allergic, Immunologic Atopic Asthma and Allergic Rhinitis Hypersensitivity pneumonitis Allergic broncho pulmonary aspergillosis (ABPA) Allergic fungal sinusitis (AFS)

2- Toxic effects of Mold exposure i.e. Mycotoxins3- Irritant effects of Mold exposure

Volatile compounds (MVOC’s) Particulates (spores, Hyphae fragments etc)

4- Immune dysfunction resulting from mold exposure5- Infections,

Immunocompromised hosts

Alternaria Morphology/CultureAlternaria Morphology/Culture

Cladosporium Morphology/CultureCladosporium Morphology/Culture

The Relationship of Molds to The Relationship of Molds to AllergyAllergy

• Alternaria sp, a common outdoor mold has been linked to asthma severity, increased likelihood of emergency room visits in sensitized individuals and even life threatening episodes of asthma

• Alternaria spores are abundant in grain growing areas the peak seasons are late summer and early fall. Approximately 80% of asthmatics may have positive skin tests to one or more fungi, up to 70% of patients with fungal allergy have positive skin tests to alternaria

• Cladosporium the commonest allergenic mold has also been implicated in asthma exacerbations.

Hypersensitivity Pneumonitis(HP)Hypersensitivity Pneumonitis(HP)

• Immunologic lung disease caused by high dose exposure, prolonged exposure or both to the causative inhalational allergens.

• The causative agents include both Thermophillic actinomycetes from moldy hay( Farmers Lung), Pigeon droppings as well as many fungi particularly aspergillus , penicillium species.

• Aspergillus species commonly present in house dust , soil particles , rotting leaves , lawn cutting leaf raking and in many occupational settings as well

• Spoiled food and moldy cheese ( Pencillium sp)

AspergillusAspergillus Morphology/cultureMorphology/culture

Penicillium Morphology/CulturePenicillium Morphology/Culture

Disease Disease

Disease

Malt workers lung disease Malt workers lung disease

Malt workers lung disease

Aspergillus species Prep of soy sauce

Soy sauce brewers disease

Aspergillus sp Poorly constructed green houses

suberosis

Aspergillus fumigatus Papermill workers lung

Penicillium sp Moldy cork dust , Cheese mold

Cheese workers lung

Penicillium sp Expansum Remodeling of wooden floors

Alternaria sp Moldy wood dust (carpenters)

Wood workers lung

HP: Clinical FeaturesHP: Clinical Features Acute, Fever cough shortness of breath,

myalgias crackles in lung fields Chronic, Progressive shortness of breath

weakness, weight loss on P/E bibasilar fine crackles CXR patchy ill defined densities, PFT’s

restrictive defect

Acute hypersensitivity pneumonitisAcute hypersensitivity pneumonitis

Chronic hypersensitivity Chronic hypersensitivity pneumonitispneumonitis

Pulmonary function tests in Pulmonary function tests in hypersensitivity pneumonitishypersensitivity pneumonitis

IGG PrecipitinsIGG Precipitins

• HP: the characteristic finding is the demonstration of serum precipitins( IgG class antibodies ) directed against offending antigens

Allergic Broncho pulmonary Allergic Broncho pulmonary aspergillosis (ABPA)aspergillosis (ABPA)

• Exposure can occur from both indoor and outdoor sources

• Occurs in patients with asthma cystic fibrosis etc• Diagnostic features include cxr infiltrates , immediate

cutaneous reactivity, peripheral blood eosinophillia, elevated total serum IgE as well as aspergillus specific IgE and IgG

• Immunologic pathogenesis related to both type I and type III hypersensitivity reactions

• Aspergillus species prevalent in house dust collected from beds

• Tx, High dose and long term steroids, role of avoidance measures uncertain

Aspergilloma lungAspergilloma lung

Patchy infiltrates ABPAPatchy infiltrates ABPA

Allergic Fungal Sinusitis (AFS)Allergic Fungal Sinusitis (AFS)

Similar to ABPA. Nasal polyps predispose, localized hypersensitivity reaction to aspergillus fumigatus in sinus cavity. Other fungi could also contribute to AFS i.e. bipolaris, curvalaria

Features include eosinophillic mucous demonstrating non invasive fungi, positive skin tests or invitro test to aspergillus

Difficult to treat and often times frequent endoscopic sinus surgery procedures is necessary

FusariumFusarium

Toxic effects of Mold ExposureToxic effects of Mold Exposure

• Mycotoxins are low molecular weight chemicals produced by certain molds

• Mycotoxin producing molds infect plants, agricultural crops (cereal grains, human foods)

• Ingestion of mycotoxin can cause serious human disease. Fusarium and aspergillus species are important examples.

(Contd)Toxic effects of Mold (Contd)Toxic effects of Mold exposureexposure

• There has been an illness described in the literature as Alimentary toxic aleukia characterized by GI symptoms, weakness and aplastic cytopenia

• The occurrence of Mycotoxicosis from exposure to inhaled mycotoxins in non occupational setting in not supported by current data and its occurrence is improbable (Bush et al 06)

Irritant effects of mold exposureIrritant effects of mold exposure

• Irritating substances produced by molds include volatile organic compounds (MVOCs) and particulates (e.g. spores, hyphae, and their components)

• MVOCs are responsible for musty odor• Mold related irritant reactions involving eyes,

upper and lower airways may be transient symptoms and signs persisting for weeks after exposure, and neurologic, cognitive or systemic complaints

• (e.g. chronic fatigue) should not be ascribed to irritant exposure (Bush et al JACI 06)

Immune DysfunctionImmune Dysfunction

• Exposure to Molds and their products does not induce a state of immune dysregulation (immune deficiency or autoimmunity)

Laboratory AssessmentLaboratory Assessment

• Patient workup

• Measurement of molds and mold products in patients environment

Patient workup, Lab assessmentPatient workup, Lab assessment

• Measurement of antibodies to specific molds has scientific merit in the assessment of IgE mediated allergic disease, HP and ABPA

• Presence of antibodies to molds can not be used as a marker to define dose timing or location of exposure.

• Testing of antibodies to mycotoxins is not scientifically validated and should not be relied on

Measurement of molds and mold Measurement of molds and mold product exposure in the patients product exposure in the patients

environmentenvironment

• Air testing is the most relevant measure of exposure and is reported as CFU or spore/m3

• Simultaneous indoor vs. outdoor fungal spore is necessary to interpret mold exposure

• Total fungal spore greater in concentration indoors than outdoor air might be evidence of increased fungal spores indoors

• Bulk surface and within wall cavity measurements don't necessarily provide a measure of exposure

Burkhard sampler/ Anderson Burkhard sampler/ Anderson SamplerSampler

Controversies in fungal diseaseControversies in fungal disease

• The overwhelming majority of claims for illness that generate litigation are based on the presence of any indoor molds and non specific symptoms

• Often times without objective physical findings and lack of specific relevant laboratory supporting data

Published mold exposure studiesPublished mold exposure studies

Reference History attributed to mold exposure

Affected building and specific mold implicated

Brunkreef 1989 6273 children respiratory questionnaires no controls

Homes total mold spores count

*Strachan 1990 Children with asthma wheezing more in home units higher mold counts. Spirometry performed

Homes total mold spores count

Johanning 1993 43 workers questionnaires no control subjects

Office building stachyboytrus species

Hodgosn 1998 197 workers questionnaires case control study control building was not tested for mold quantitation

Office building aspergillus penicillium stachyboytrus

*Santilli and rockwell 2003 Rhinitis questionnaire 85 students and teachers

Two schools total mold spores

Cooley 1998 622 adult workers at 48 schools with indoor air quality complaints no control subjects

Schools penicillium stachyboytrus

Sick Building SyndromeSick Building Syndrome

• The term "sick building syndrome" (SBS) is used to describe situations in which building occupants experience acute health and comfort effects that appear to be linked to time spent in a building, but no specific illness or cause can be identified.

Sick Building SyndromeSick Building Syndrome

• A 1984 World Health Organization Committee report suggested that up to 30 percent of new and remodeled buildings worldwide may be the subject of excessive complaints related to indoor air quality (IAQ)

• The causes usually inadequate ventilation, biological contaminants, chemical agents and the symptoms improve on leaving the environment

Stachybotrys Stachybotrys

• 45 young infants (most under 6 months old), in the eastern neighborhoods of Cleveland, who had Pulmonary Hemorrhage (16 kids died) appears to be caused by something in their home environments, most likely toxins produced by an unusual fungus called Stachybotrys chartarum or similar fungi

Centers for Disease Control and Prevention. Acute Pulmonary Hemorrhage/Hemosiderosis among Infants- Cleveland, January 1993-November 1994. Morbidity and Mortality Report, Vol. 43, No. 48, December 9, 1994

The Case of StachybotrysThe Case of Stachybotrys

• Requires substantial humidity for growth• Grows on cellulose rich media-examples

wall paper, fiber board , gypsum, insulation materials, wood pulp, Lint, carpet, cereal grains, plant, debris flood damaged buildings with high humidity

• Produces mycotoxins( trichotecenes)• Similar mycotoxins produced by other

fungi i.e. fusarium, acretonium

• In 1931(Ukraine) there was an epidemic amongst horses who developed stomatitis, rhinitis, conjunctivitis, pancytopenia, neurologic disorders, deaths( Massovie Zabouluanie)

• Trichothecenes mycotoxins inhibit protein synthesis , impair immune function , prolong skin graft survival, hemorrhagic inflammatory lung injury.

• (Mahmoudi M, Gershwine. Jr of Asthma 37(2)191,2000)

• The contaminated buildings had considerably higher indoor mold counts than outdoor counts( IOM report 2004)

• Several clinical studies report significant respiratory disease in schools, office buildings, court houses and homes in many instances Stachyboytrys was isolated (Goldstein GB, Jaci Sep 2006)

Air conditioner Mold ContaminationAir conditioner Mold Contamination

• Automobile air conditioner contamination with molds and exacerbation of respiratory allergies; Kumar et al NEJM 1984

• Hypersensitivity pneumonitis due to air conditioner contamination; Kumar et al NEJM 1983

Mold remediationMold remediation• DRY QUICKLY

– Dry items before mold grows, if possible.  In most cases, mold will not grow if wet or damp items are dried within 24-48 hours

• ASSESS MOLD PROBLEM

– Are there existing moisture problems in the building? – Have building materials been wet more than 48 hours? – Are there hidden sources of water, or is the humidity high enough to cause condensation?

• REMEDIATION PLAN

– How the water or moisture problem will be fixed so the mold problem does not recur. – How the moldy building materials will be removed to avoid spreading mold

• MOLD REMEDIATION PROCEDURES

– Damp wipe with bleach and detergent mixed one cup to a gallon of water avoid mixing with ammonia ( i.e. cleaning detergents)

– Hepa vacuums

Rebuttal of position paper on Mold Rebuttal of position paper on Mold AllergyAllergy

• (JACI-correspondence, vol 118, No3, sep 2006)• The authors of the position paper had conflict of interest• Respirable trichotehecene mycotoxins can be

demonstrated in the air of stachybotrys chartarum contaminated buildings

• Trichothecene mycotoxin has been shown to cause nausea vomiting, low blood pressure, drowsiness, ataxia, mental confusion

• Similar symptoms reported by individuals from sc-contaminated buildings (Straus, Wilson, JACI 2006)

• 93 residents of apt. complex with chronic visible mold contamination reported multiple symptoms (cough 49%, rhinitis 44%, wheeze 31%, headache 41%.

Adverse Health effects of Indoor Adverse Health effects of Indoor Mold exposureMold exposure

• “ We agree the mold exposure has become a litigious issue. But are we as physicians to choose sides ? Or are we to evaluate objectively the alleged effects of toxic mold exposure? We suspect your interpretations of where and what is not supported by scientific evidence might at least in part represent an agenda for the defense”

(Lieberman A, JACI Sep 2006)