Expert Panel Tackles Toxic Molds

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EXPERT PANEL TACKLES THE HEALTH RISKS OF TOXIGENIC MOLDS INDOORS

Over the years, health departments have investigated community concerns

about the health effects of poor indoor air quality. Many factors contribute

to poor indoor air quality which may result in a variety of symptoms. The

role of the health department is to investigate and determine which factors

contribute to the symptoms experienced and to initiate controls. In the case

of mold contamination of the indoor environment, assessment of health risk

is often difficult. Determining health risk to individuals in contrast to

risk to a community presents a public health challenge.

In order to assist health departments, the Environmental Health and

Toxicology Unit (EHTU) of the Disease Control Service, Public Health Branch,

convened a panel of experts in respiratory medicine, allergy, mycology,

epidemiology and community medicine, to review the issue of mold

contamination indoors. What follows is the Expert Panel Report which

includes a scientific summary, points of consensus, response to specific

questions, and recommendations.

Expert Panel Report

Scientific Summary

The health risks of molds in indoor environments are associated with the

following potential pathogenic mechanisms:

1. allergic (IgE-mediated asthma) and other immunemediated mechanisms

(hypersensitivity pneumonitis);

2. toxic and irritative mechanisms (eg. mycotoxins, glucans, volatiles

(pulmonary hemosiderosis, non-specific respiratory and flu-like symptoms);

3. infectious mechanisms (eg. illnesses in immunocompromised individuals

from normally non-pathogenic organisms (asperigillosis, zygomycosis)

4. carcinogenic mechanisms (eg. aflatoxins).

The evidence for the clinical effects of exposure to indoor air molds is

clear for conditions such as asthma, hypersensitivity pneumonitis, fungal

infections, organic dust toxic syndrome and aflatoxin-related cancers.

However, the association between mold and non-specific symptomatology or

more precisely, the direct chemical effects of mycotoxins and non-specific

clinical syndromes (including respiratory and other symptoms), is less well

understood.

· Characterization of human exposure to molds in residential settings is

difficult with current methodologies. Difficulties relate to the counting of

spores, multiple species of molds that may be growing in indoor

environments, and determination of the fraction of viable spores. In future,

in vitro techniques based on relevant biomarkers may provide better exposure

information.

· Methods for measuring the production of mycotoxins in home settings are

inexact and studies often rely on proxy measures such as occupant-reported

mold or water damage.

· The symptoms and reported health effects recorded in these studies are

difficult to validate objectively.

At this time it is not possible to definitely conclude that molds are

responsible for the wide variety of reported symptoms.

Molds are ubiquitous in indoor and outdoor environments. Because of the

limitations in quantifying risk, the burden of mold-related illness in the

population is difficult to determine. For illnesses such as asthma for which

there is good evidence of a mold-related etiology, the population burden is

judged to be small. However, there are situations in which significant

quantities of mold may develop resulting in significant health risks.

Such situations are often easily remediable. Remediation of a known

amplifier (an indoor substrate where fungal growth is occurring) rests on

removal of the amplifier and moisture control. Fungicides have limited if

any value in these situations. Remedies for situations in which mold has

accumulated over time are less straightforward. The current recommendations

of HEPA (high efficiency particulate arresting) filter vacuuming and common

sense cleaning are usually effective provided moisture and amplifier control

are also undertaken. The CMCH booklet, " Clean-up procedures for mold in

houses " , provides the details of these clean-up procedures.

Consensus points

· Epidemiological studies have demonstrated a clear association between

the presence of molds in homes and a number of respiratory and other

symptoms.

· Many of the symptoms that have been associated with molds are

nonspecific, and have also been associated with a number of other factors.

· Clinical evidence indicates that both asthma and hypersensitivity

syndromes can be caused by exposure to mold in susceptible individuals.

· In vitro studies on fungal mycotoxins and glucans suggest a biological

basis for human respiratory effects.

· Although molds can cause clear health effects under certain

circumstances, the burden of illness in the general population remains to be

clarified.

· The nature of the dose-response relationship for symptoms associated

with molds is not clear. The possible existence of a threshold dose below

which health effects would not occur needs to be considered in assessing

population health risks.

Panel responses to specific questions

1. Are the health impacts of indoor air molds sufficient to be called a

health hazard under the Health Protection and Promotion Act?

Under the HPPA, a health hazard means " (i) a condition of a premises, (ii) a

substance, thing, plant or animal other than man, or (iii) a solid, liquid,

gas or combination of any of them, that has or is likely to have an adverse

effect on the health of any person " .

Epidemiological and clinical evidence clearly indicates that molds

contribute to respiratory and other symptoms. However, such effects tend to

occur in susceptible individuals, or when exposures are high. Consequently,

the Panel concluded that molds can pose a health hazard under certain

conditions within the context of the HPPA.

2. What conditions must be present to reasonably anticipate that there is

a health hazard?

With the possible exception of infectious or allergic diseases, it is

generally difficult to attribute adverse health effects observed in

individuals to specific environmental exposures, including exposure to

indoor air molds. However, the Panel was able to identify factors that

increased the risk of an adverse health effect occurring following exposure

to indoor air molds. Adverse health effects have been observed with

increased frequency in susceptible individuals subjected to high levels of

exposure for example infants who developed pulmonary hemosiderosis. High

inoculum potential also increases risk. The more noxious (high potential for

mycotoxin production) species of mold pose the greatest risks.

3. What factors should be considered in host response?

A number of factors can affect individual response to exposure to indoor air

molds. Infants, asthmatics, individuals with pre-existing respiratory

conditions, and individuals with compromised immune systems are likely to be

at increased risk.

4. What conditions can a Medical Officer of Health include in order to

mitigate the health hazard?

Indoor air molds can be controlled in a number of ways. In general, indoor

air molds can be reduced by eliminating conditions favourable to growth.

Specifically, reducing water availability (including leaks and condensation)

to the organisms will generally reduce growth. Disinfection or removal of

affected materials, or materials in which molds may proliferate, are

effective in eliminating molds. The Panel noted that because of the

uncertainty associated with the risks of molds, mitigation actions need to

be developed in the context of each situation.

Recommendations

· Because of the observation of pulmonary hemosiderosis among children

exposed to high levels of mold in Cleveland, it may be worthwhile to

investigate the occurrence of this condition in the Toronto area. If an

excess of pulmonary hemosiderosis were observed, the role of Stachybotrysin

the etiology of this condition should be investigated.

· The panel noted that there remain a number of uncertainties concerning

the relationship between molds and health effects and that there continue to

be ongoing investigations worldwide. The panel recommends that this issue be

reviewed again after an appropriate interval.

As recommended by the Expert Panel, the EHTU will examine the prevalence of

pulmonary hemosiderosis in infants in Ontario and pursue appropriate follow

up studies. The Public Health Branch thanks the Expert Panel for their

participation.

Panel Members:

Dr. Krewski - Chair

Bureau of Chemical Hazards

Environmental Health Directorate

Health Canada

Dr. Tarlo

Allergy

University of Toronto and Toronto Hospital

Dr. Sales

Respiratory Medicine

University of Ottawa and Ottawa General Hospital

Dr. Vivek Goel

Medical Epidemiology

University of Toronto

Dr. Summerbell

Mycologist

Ministry of Health

Dr. Ross Upshur

Community Medicine

University of Toronto

CONTACT

, MEd, CPHI©

Environmental Health and Toxicology Unit

Disease Control Service

Public Health Branch

Telephone: 416 327-7427

Facsimile: 416 327-7439

This article appeared in the Public Health & Epidemiology Report Ontario

(PHERO) Newsletter, Volume 8, Number 2, February 28, 1997. PHERO is

published monthly by the Public Health Branch, Ministry of Health, North

York. Telephone: 416 327-7623.

PULMONARY HEMOSIDEROSIS IN ONTARIO INFANTS, 1991-1995

Abstract

Pulmonary hemosiderosis is a rare condition of infancy. In 1994, a cluster

of cases of this disorder occurred in Cleveland. This cluster was

investigated by the local health department and the Centers for Disease

Control in Atlanta. The investigation demonstrated a strong association of

the cases with water damage (flooding). The toxigenic mold, Stachybotrys

atra, was found in all of the infants' homes, though its concentration was

not statistically associated with the cases. Other mold species were also

identified as were low concentrations of several household pesticides.

There is a chain of evidence in these cases which points to the potential

for mold as a contributory etiologic factor for pulmonary hemosiderosis. We

began to investigate its occurrence in Ontario in order to determine if

there is any evidence of clustering of this rather rare condition here. This

report is the result of a preliminary examination of hospital separations in

Ontario, focusing on infants under one year of age and a diagnosis of

pulmonary hemosiderosis. The project was designed to be completed in a

timely and cost effective manner.

Ontario hospital separations from 1991-1995 were screened for infants

admitted to hospitals with the ICD-9 codes of 516.1 (idiopathic pulmonary

hemosiderosis) and/or 275.0 (disease of iron metabolism). A potential case

was an infant who had no known secondary cause of pulmonary

hemorrhage/hemosiderosis after review of other diagnoses in the separation

date file.

The results demonstrate that an unusual number of cases (10) occurred in the

1991 fiscal year while none occurred in the other years reviewed in this

study. We believe that the Ontario hospital separations data base should be

more carefully examined using the information gained in the initial survey.

A geographic analysis of cases with an extension of the search for other ICD

codes for pulmonary disease in infants may support a more intensive research

project examining the environmental causes of pulmonary

hemorrhage/hemosiderosis in Ontario infants. Should this association be

confirmed, information about the prevention of exposure of children to moldy

homes will require more aggressive dissemination by public health and other

agencies.

Introduction

In December, 1994 the CDC reported a cluster of eight cases of idiopathic

pulmonary hemosiderosis diagnosed at the Rainbow Babies and Children's

Hospital (RBCH) in Cleveland from January 1993-November 1994. During the

preceding ten years only 3 cases of this disorder had been diagnosed at the

same hospital.(1)

A case control study was performed using 10 case-infants and 30 age-matched

controls from the same area in Cleveland(2,3). The study found a decreased

incidence of breastfeeding (odds ratio [OR]=0.2; 95% confidence interval

[CI]=0-1.2) and an increased incidence of smoking for the case-infants

(OR=7.9; CI=0.9-70.6) which did not achieve a level of statistical

significance. However, all ten of the case-infants had resided in homes

where severe water damage had occurred in the 6 months prior to admission

versus 7(23%) of the 30 controls (OR=16.3; CI=2.6-infinity). Case infants

were also more likely to have had close relatives with pulmonary hemorrhage

(OR=33.14; CI= 5.1-infinity). Lastly, 50% of the infants had recurrent

pulmonary hemorrhage after returning to their homes.

Visual inspection of the children's homes, fungal quantification and fungal

identification were then performed. There was a higher concentration of

fungi in the case infants' homes (OR=1.6; CI=1.0-30.8). Among the molds in

the homes was Stachybotrys atra. It is a candidate causative organism for

infant pulmonary hemorrhage because its toxins have been implicated in

hemorrhagic disorders in animals. The study suggests that environmental risk

factors may have contributed to pulmonary hemorrhage in the case-infants.

All of the ten infants presented with hemoptysis associated with pallor and

an abrupt cessation of crying in the absence of fever. Extensive

investigation failed to find a specific etiology for the hemoptysis and the

diagnosis of idiopathic pulmonary hemosiderosis was therefore assigned.

TABLE 1

Causes of Hemoptysis in Children

Infection

Bacterial

Lung abscesses

Necrotizing pneumonia

Tuberculosis

Bronchiectasis (cystic fibrosis immune

deficiency, immotile cilia)

Fungal

Actinomycosis

Aspergillosis

Coccidioidomycosis

Histoplasmosis

Parasitic

Echinococcosis (hytadid disease)

Paragonimiasis

Strongyloidiasis

Foreign Bodies

Congenital Defects

Cardiovascular

Congenital heart defects

Absent pulmonary artery

Ateriovenous malformation

Hemangiomatous malformation

Telangiectasia (Osler-Weber-Rendu

Syndrome)

Other

Pulmonary sequestration

Bronchogenic cyst

Intrathoracic enteric cyst

Vasculitis

Periarteritis nodosa

Adapted from Rosenstein(4)

Autoimmune Disorders

Wegener's granulomatosis

Pulmonary hemosiderosis

Milk Allergy

Goodpasture's syndrome

Collagen vascular disease

Trauma

Compression or Crush Injury

latrogenic

Postsurgical

Diagnostic lung puncture

Transbroncial biopsy

Inhalation of Toxins

Neoplastic Conditions

Endobronchial Metastases

Primary Lung Tumors

Benign (hamartoma, neurogenic tumors)

Malignant (bronchial adenoma,

bronchogenic carcinoma, pulmonary

blastoma)

Endometriosis

Drug Induced

Propylthiouracil

Pulmonary Embolism

Hemoglobinopathy With Pulmonary Infarct

Factitious

Hemoptysis, defined as the expectoration of blood or blood tinged sputum, is

unusual in the pediatric age group. Massive hemoptysis, as occurred in the

case-infants in Cleveland is even rarer. The most common cause of hemoptysis

in children is infection, followed by aspiration of a foreign body (not

necessarily for infants). Other important causes include cardiac

malformations, vascular malformations, and autoimmune disorders(4).

Pulmonary hemosiderosis is an unusual cause of infant pulmonary hemorrhage

and is estimated to account for less than 5%(2) of infant cases. A detailed

list of the causes of hemoptysis in children is given in Table 1.

Pulmonary hemosiderosis is a nonspecific finding that usually indicates

previous hemorrhage or aspiration of blood. Essentially, blood iron

phagocytosed by alveolar macrophages is stored within them as hemosiderin.

The causes of pulmonary hemosiderosis are usually divided into secondary

cardiac or systemic causes (listed in Table 1 for hemoptysis) and primary

disorders intrinsic to the lung(5). In its primary form there is no

demonstrable cause for pulmonary hemorrhage. Often primary hemosiderosis is

divided into four variants: (1) an isolated form; (2) a form associated with

allergy to cow's milk; (3) a form associated with myocarditis or

pancreatitis; and (4) a form associated with progressive glomerulonephritis

(Goodpasture's syndrome)(6). Some others only classify the first form of the

disease as idiopathic pulmonary hemosiderosis (IPH)(5) whereas others group

all four into IPH(6). Either way, IPH is the most common type of pulmonary

hemosiderosis. Generally, infants who were previously healthy and then have

chronic recurring episodes of pulmonary hemorrhage of unknown cause are

diagnosed as having IPH(3). Pulmonary hemosiderosis can present in one of

two ways: (1) fulminant onset with recurrent acute hemoptysis (as in the

Cleveland cluster); or (2) insidious onset with anemia, pallor, weakness,

and lethargy(6).

Cassimos et al. described 30 cases of IPH in Greece over a 20 year

period(7). The cases occurred in household clusters where children were

sleeping in rooms near stored grain. The authors suggested that the

illnesses may have been associated with chronic pesticide exposure. More

recently, the clusters in Cleveland suggest another environmental cause of

IPH; exposure of susceptible infants to molds, specifically, Stachybotrys

atra. A search of the Ontario hospital separation data base was done to

explore in a timely and cost-effective manner if there are unrecognized

clusters of IPH that may be due to an environmental exposure.

Methods

The Ontario hospital separations data base was searched for children under

five years of age at the time of hospitalization with diagnosis of

idiopathic pulmonary hemosiderosis (ICD-9 516.1) and/or disease of iron

metabolism (ICD-9 275.0). The fiscal years 1991-1995 were searched.

These individual records were then examined to see if the cause of pulmonary

hemosiderosis was attributable to a known cause of infant pulmonary

hemosiderosis according to the exclusion criteria used by the CDC(8). Known

causes of pulmonary hemorrhage/hemosiderosis in infants include: bacterial

pneumonia; septicemia; tuberculosis; bronchiectasis; pulmonary malignancy;

Gaucher's disease; Wegener's granulomatosis; cardiac anomalies; and vascular

anomalies. Separations of pulmonary hemosiderosis not meeting the exclusion

criteria were counted as being potential cases.

Results

A total of 23 separations were found that had at least one of the two ICD-9

codes used in the search. There were no potential cases for the years

1992-1995. On average there were 2.25 separations found by the search

ranging from 1 to 4 for any given year between 1992 and 1995. In 1991 there

were 10 potential cases from a total of 14 separations identified in the

search. Significantly, none of these potential cases reported pulmonary

hemorrhage or hemoptysis. (Table 2).

Discussion

This data review was carried out following reports that an outbreak of

infant pulmonary hemorrhage/hemosiderosis in Cleveland, OH was associated

with water damage and high levels of the mold in the children's homes;

Stachybotrys atra was one of the molds identified in the homes of affected

children. Ontario has much of its population in cities and towns which, like

Cleveland, borders one of the Great Lakes and has a similar climate.

Therefore, it is quite possible the same environmental conditions are

present in homes in Ontario where infants are found and causing pulmonary

hemorrhage/hemosiderosis in a number of susceptible individuals.

This study was undertaken to explore that possibility. Screening the

provincial hospital separation data for idiopathic pulmonary hemosiderosis

can quickly and inexpensively determine if there was potentially a cluster

of these cases. If that is the case, follow up with a geographic analysis

and an examination of risk factors in each child can potentially discover if

the case could be attributed to water damage of homes and/or botrys

exposure. Given the small number of potential cases and the specificity of

the diagnosis, the approach taken was deemed the most appropriate first

step.

Table 2

Hospital Separations by Fiscal Year: Children Under 5 Years

with ICD-9 Codes 516.1/275.0

Fiscal Year Separations with Number with Number of

ICD-9 code 516.1 or 275.0 Pulmonary Hemosiderosis Potential Cases

1991 14 10 10

1992 2 1 0

1993 2 0 0

1994 1 0 0

1995 4 1 0

Results of search of Ontario hospital's separation data. Children 5 years of

age or younger who were diagnosed with ICD-9 codes 516.1 (idiopathic

pulmonary hemorrhage) and/or 275.0 (Disease of iron metabolism) were

screened from the data base. Potential cases were those children with

pulmonary hemorrhage/hemosiderosis who had no known cause for this disorder

based on the separation data.

The results suggest a time-limited cluster of cases of IPH 1991. Ten

potential cases appear in this year versus none in the following four years.

None of these potential cases is reported to have pulmonary hemorrhage or

hemoptysis. It is not known if this is because this symptom is truly absent

(insidious IPH) or not captured by the database (fulminant IPH). If these

ten cases did not have hemoptysis, then they would be quite different from

the Cleveland case-infants' presentation. Does this mean a new form of the

same phenomenon, a new phenomenon, or merely coincidence?

As a follow up to this study, we will examine the hospital separation data

base further by extending the number of years searched (1988-1997), by

including several other ICD codes which may capture the diagnosis of IPH,

and by limiting the search to infants under 12 months of age. A broader

search of the database extending the years and the separation diagnostic

codes is needed to clarify the preliminary results obtained here. The

outcome of this second search may warrant a more detailed examination of the

situation (such as a chart review) and epidemiologic study (such as a

case-control study) which could provide more definitive evidence for this

rare disease and novel association.

Source:

Shapiro, MD

Community Medicine Resident

University of Toronto

Contact:

Lesbia F. , MD

Senior Medical Consultant

Environmental Health and Toxicology Unit

Population Health Service

Public Health Branch

smith99@...

References:

1. CDC. Acute pulmonary hemorrhage/hemosiderosis among infants- Cleveland,

January 1993-November 1994; MMWR 1994; 43(2): 881-883.

2. CDC. Update: pulmonary hemorrhage/hemosiderosis among

infants-Cleveland, Ohio, 1993-1996. MMWR 1997; 46(2): 33-35.

3. Montana E, Etzel RA, Allan T, Horgan TE, Dearborn, DG. Cleveland, Ohio,

1993-1996. MMWR 1997; 46(2): 33-35.

4. Montana E, Etzel RA, Allan T, Horgan TE, Dearborn DG. Environmental

risk factors associated with pediatric idiopathic pulmonary hemorrhage and

hemosiderosis in a Cleveland community Pediatrics 1997; 99(1): e5. World

Wide Web site http://pediatrics.org/cgi/content/99/1/e5

5. Rosenstein BR. Hemoptysis. In: Hilman, B.C. ed. Pediatric Respiratory

Disease: Diagnosis and Treatment. Philadelphia, PA: WB Saunders Co; 1993:

533-543.

6. Cutz E. Idiopathic pulmonary hemosiderosis and related disorders in

infancy and childhood. Perspect. Pediatr. Pathol. 1987; 11: 47-81.

7. Levy J. and Wilmott, R. Pulmonary Hemosiderosis. In: Hilman, B.C. ed.

Pediatric Respiratory Disease: Diagnosis and Treatment. Philadelphia, PA: WB

Saunders Co; 1993: 543-549.

8. Cassimos CD, Chryssanthopoulos C, Panagiotidou C. Epidemiologic

observations in idiopathic pulmonary hemosiderosis. J. Pediatr. 1983:

102(5): 698-702.

9. CDC. CDC study of acute pulmonary hemorrhage/hemosiderosis in infants.

World Wide Web site http://p e d s c c m . w u s t l . e d u / R E S E A R C

H / Pulmonary_hemorrhage.html

This article appeared in the Public Health & Epidemiology Report Ontario

(PHERO) Newsletter, Volume 9, Number 3, March 27, 1998. PHERO is published

monthly by the Public Health Branch, Ministry of Health, North York.

Telephone: 416 327-7623.

Population Health Service Comment

Mold growth indoors continues to be an issue of growing concern because of

its potential relationship to adverse health effects. In the past year,

several instances of large-scale mold contamination in buildings have come

to the attention of public health departments. These have always occurred

with flooding inside the building or breaching of walls from the outside. In

the aftermaths of recent weather related disasters (i.e. flooding, ice

storm), there are likely to be many instances of premises developing mold

problems. Stachybotrys atra has received quite a bit of attention in the

media. However, as is pointed out in the article above, it may not be the

cause of any particular health problem if it is found in a premise. We

highly recommend that staff dealing with this issue review the articles

referenced in this report, in particular, those by Montana and Etzel, which

clearly describe the relationships found between dampness, mold and infant

illness. In the light of these reports and the media attention which the

mold issue has received, public health staff can anticipate increased

community concern and demand for information.

Three publications provided by the Public Health Branch to public health

departments will be useful in anticipating problems and responding to

concerns: The Expert Panel on the Health Risks of Toxigenic Molds (PHERO

1997), Indoor Air Quality Resource Document, and the CMHC booklet, Clean-up

Procedures for Mold in Homes. Public Health documents can be forwarded to

you electronically by contacting the branch directly at the e-mail addresses

listed with the contacts.

Sources and Contact:

, MEd, CIPHI

Senior Inspection Consultant

Environmental Health and Toxicology Unit

Population Health Service

Public Health Branch

powell99@...

This article appeared in the Public Health & Epidemiology Report Ontario

(PHERO) Newsletter, Volume 9, Number 3, March 27, 1998. PHERO is published

monthly by the Public Health Branch, Ministry of Health, North York.

Telephone: 416 327-7623.