54. Building-Related Disease

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BUILDING-RELATEDDISEASES

Michael Hodgson, M.D., M.P.H.U.S. Department of Veterans Affairs

Occupational Health Program

Veterans Health Administration

Washington, DC

Building-related diseases (BRD) may be classified, among other ways, by mechanisms ofdisease, as is traditional in medical texts; by presenting symptoms, as is useful in the diag-nosis and treatment of patients; or by source and etiologic agent, which are usefulapproaches in engineering and regulatory strategies. Some redundancy will occur in allthree classification systems. This chapter will present diseases according to the first cate-gorization (see Table 54.1).

Users of this text should remember the distinction between the sick-building syndrome(SBS) and what is often called building-related illness (BRI). The latter represent clearlyrecognized clinical conditions with operational criteria (i.e., medical conditions for whichwide agreement exists on how to make a diagnosis). Even for these, though, there may be

disagreement on individual diagnoses, on best treatment strategies (as even national con-sensus guidelines may fail to address adequately specific occupational or environmentalhealth aspects of treatment strategies such as removal from work or the importance of expo-sure control), and on the true cause. On the other hand, the SBS remains a term withoutoperational criteria. Although the epidemiology of building-related complaints has beendescribed since the mid-1980s (Finnegan 1984, Kreiss and Hodgson 1984, Mendell 1993)and dose-response relationships have been recognized for over 10 years (Hodgson et al.1991), few studies have examined the mechanism of symptoms in an epidemiologic con-text. Such attempts for eye and nasal symptoms will be described later. Nevertheless,

Jaakola (1998) suggests that the term SBScurrently represents a construct for discussionpurposes only. As the mechanisms for the various symptoms, from odor and irritationthrough headaches and allergies, are clarified, researchers will characterize the nature andseverity of the underlying conditions and support the use of diagnostic tests in the clinicaldiagnosis of individuals. Individual components of what is now labeled SBS may becomebuilding-related illnesses.

CHAPTER 54

54.1

Copyright 2001 by The McGraw-Hill Companies Retrieved from: www.knovel.com


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54.2 ASSESSING IAQ

TABLE 54.1 Disease Categories

Disease Symptoms Mechanisms Diagnostic Criteria

Rhinitis, sinusitis Stuffy or runny nose; Allergy (IgE) Eosinophilic granulocytes inpostnasal drip; nasal secretions

sinus congestion; Specific changes on nasalnosebleeds provocation symptoms

Irritation None described

Allergic fungal Stuffy nose, postnasal Allergy (IgE), other? CT-scan evidence of

sinusitis drip, headache inflammation,eosinophilic mucous,fungal hyphae visible onstaining

Asthma (airways Coughing, wheezing, Allergy (IgE, IgG) Airways hyper-reactivity (moredisease) shortness of breath, than 15 percent change in FEV1)

chest tightness Reversibility of obstructionwith bronchodilators

Pharmacologic See above, history of exposureirritant during onset of asthma

Hypersensitivity Cough, shortness of Type IV allergy (cell- Granulomas on biopsy,pneumonitis breath, muscle aches, mediated immunity) reversible restrictive changes,feverishness (DLCO, TLC, CXR), CT

scan, thin-section CT scan

Organic dust toxic Cough, shortness of Endotoxin response DLCO, TLC, spirometry,syndrome (inhala- breath, muscle aches. (macrophage white blood celltion fevers) feverishness receptor based effect) count elevations

Contact dermatitis Dry, itching, scaling, Type IV skin allergy Inspection, skin biopsy,(allergic) red skin patch testing

Irritant contact Dry itching or Irritation Inspection, skin biopsydermatitis weeping skin

Contact urticaria Red, irritated skin, Type I allergy Inspection, RAST or skin pricetesting hives

Conjunctivitis Eye irritation, dryness, Type I allergy Inspection, RAST or skin prick(allergic) tearing testing, tear-film break-up

time, conjunctival staining

Conjunctivitis Eye irritation, dryness, Irritation Inspection, tear film break-up

(irritant) tearing time

CNS toxicity Headaches, Carbon monoxide Elevated carboxyhemoglobincognitive impairment (COhgb)

VOCs Abnormal neuropsychologicaltests

Heat, noise Calculated heat indices outsiderange; noise levels abovecomfort range



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BUILDING-RELATED DISEASES 54.3

TABLE 54.1 Disease Categories

Diagnostic tests Linkage strategies Causes

Nasal secretions; eosinophiles IgE-based: RAST or skin Sensitizers in the workplaceCT scan for chronic inflammatory prick tests; nasal challenge (allergens) including molds,

changes symptom patterns carbonless copy paper, photo-Acoustic rhinometry active processes (toners), andRhinomanometry (anterior and secondary exposures, e.g., cat

posterior dander brought to work onclothing; pesticides (OPs,pyrethrin)

None described Symptom patterns Irritant exposures, including clean-ing agents, volatile organic com-pounds, dust, molds and bacteria,low relative humidity

Surgical tissue for eosinophilic Recurrences at work, same Bioaerosols at work

staining in mucous, fungal bodies organisms in workplace

Physical examination Temporal relationship of lung As allergic rhinitis irritant expo-Spirometry with bronchodilators function decrements at sures, including cleaning agents,Methacholine challenge work (PEFR, spirometry) volatile organic compounds,Substance specific challenge Immunologic tests (skin dust, molds and bacteria, low

prick tests, RAST tests) relative humiditySee above As aboveAs above Clinical history

Granulomas, restrictive changes in Physiologic linkage (acute Molds and thermotolerant bacterialung function in a convincing disease: reversible patterns) related to moistureclinical setting Immunologic linkage: IgG

exposure only; lymphocytetransformation to specificantigens

Bronchial lavage, DLCO, TLC, Temporal pattern and Gram negative bacteria, molds,spirometry, white blood cell exposure documentation polymers in thermal degradationcount elevations related to work

Inspection, skin biopsy, patch testing Patch testing, temporal pattern Formaldehyde, molds, laser toners,Behenic acid (photoactive

process)Clinical history, lactic acid Temporal pattern Office products, VOC based

application (stinger test)

Clinical history, RAST test Temporal pattern; RAST or Office productsskin prick test

Punctate conjunctivitis, shortened Clinical impression Molds, sensitizerstear film break-up time, RAST orskin prick testing, cobblestoningon physical examination

Inspection, tear film break-up time Clinical impression Irritants (VOCs, dust, low relative

humidity), failure to blink atVDUs

Neuropsychological tests, COhgb 3% in nonsmokers, Fossil fuel sources: HomeCOhgb levels 8% in smokers attached garages, backdrafting

appliances, barbecues; commer-cial/public buildingsentrainedexhaust, indoor CO sources

Abnormal neuropsychological tests Abnormal neuropsychological Imbalance between local VOCtests source and exhaust ventilation

None Clinical impression Inadequate control strategies



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54.1 GENERAL APPROACHES

Diseases related to indoor environments are treated no differently than are conditionspotentially related to other environmental and occupational exposures (see Table 54.2). Thebasic approach includes the following steps:

G Document disease

G

Document exposureG Define linkage (or exclusion) criteria

G Develop a management plan

For reasons described below, this approach has not been as successful in indoor environ-ments as elsewhere, and the scientific basis for this approach is often still missing.

Document Disease

Physicians and other health care providers make a diagnosis of a condition based primarilyon symptoms. Over 75 percent of conditions encountered in primary care need no furtherdocumentation (Peterson 1992). In fact, for many there is little objective evidence on anindividual basis. In the setting of lawsuits and workers compensation proceedings, physi-cians are often asked to provide evidence. It is therefore important to seek objective signson physical examination and measurements of abnormal organ function in laboratory test-ing, which can often be found. Even then, a few patients with symptoms will have evidenceof some physiologic or immunologic process without meeting a set of diagnostic criteriafor any specific condition.

At times, even in symptomatic patients, tests are negative. That all tests may have falsenegative results is a fundamental truth, defined in the relationships of sensitivity, speci-ficity, and predictive value. As a test identifies a greater proportion of individuals correctlyas having a specific outcome, it also identifies more individuals without those characteris-tics. As tests are more precise, and identify fewer false positive results, more individualswith the condition are missed. In the absence of economic conflicts, physicians feel verycomfortable ignoring unexpected and unlikely results. In the setting of workers compensa-tion proceedings and litigation, where economic outcomes are implicit, physicians are oftenat a loss to explain their reasonable approaches. Elsewhere, evidence-based medicine seeks

54.4 ASSESSING IAQ

TABLE 54.1 Disease Categories (Continued)

Disease Symptoms Mechanisms Diagnostic criteria

Legionnaires Coughing, phlegm Legionella exposure, Four-fold rise in antibody titers,

disease production, fevers susceptible host culture of same Legionellastrain from source as from tis-sue, epidemiologic clustering

Tuberculosis Coughing, phlegm Infection with Isolation of organisms,production, fevers, Mycobacterium positive skin test withweight loss tuberculosis typical chest x-ray pattern

FEV1 forced expiratory volume in the first second, PCR polymerase chain reaction-based lab test, RAST radioal-lergosorbent test, DLCO single breath carbon monoxide diffusing capacity, TLC total lung capacity, CXR chest x ray,and PERF = peak expiratory flow rate..



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consensus from a broad range of published literature to establish diagnostic and treatmentguidelines. Such literature is often still missing for diseases related to indoor environments,as it is for much of occupational and environmental disease. This chapter will focus pri-marily on the management of building-related diseases and provide evidence where we rec-ognize it.

Document Exposure

The discipline of industrial hygiene grew out of physicians needs to understand the expo-sures that made their patients sick and of engineers need to evaluate the control strategiesunderlying engineering processes. Since the early part of this century, a major goal in thefield has been the definition oflimits, criteria levels below which no adverse health effectswere likely to occur. Setting such limits had as a consequence the development of evalua-tion methods, later also used for enforcement. Table 54.2 represents a compilation of expo-sure levels commonly used for the traditional occupational environment, for ambientenvironmental conditions, and for indoor environments. For building-related diseases, theexposures remain poorly defined for three reasons.

First, the specific pertinent component remains unknown for many agents. Therefore,in hypersensitivity pneumonitis, it is unclear whether to measure for fungi with viable sam-plers (using culturable agents as the outcome), spore traps (using visible spores), immuno-logical testing (in the absence of knowing which antigen), or biological assays such asendotoxin (which may trigger existing diseases without being the true cause). Second, evenfor diseases as clearly linked to environments with physiologic testing as hypersensitivitypneumonitis and asthma, the correct analytical methods are unclear. Because it is unclearwhether only culturable (viable) particles are important for sensitization to fungal agents,and which components of other antigens, such as dust mites, are important, the appropriate

analytical methods are unclear. Third, the best sampling approaches remain undefined. Theexposures required for sensitization (duration, intensity, specific agent, and cofactors) ortriggering of attacks are generally unknown, despite universal beliefs about the importanceof dose-response relationships.

Similar considerations arise for the spectrum of volatile organic compounds, for noiseand vibration, and for other exposures in the indoor environment. For this reason, tradi-tional industrial hygiene approaches (identification of the primary pollutant of concern,quantitative assessment, and comparison with a criterion level) have uniformly been unsuc-cessful in solving problems in the indoor environment. The evolution of building sciences


TABLE 54.1 (Continued)

Diagnostic tests Linkage strategies Causes

Fourfold rise in antibody titers, Same organisms from putative Aerosol dispersion,

culture from human samples, source and from patient, aspirationepidemiology clinical pattern

PCR similarity between organism PCR similarity betweenfrom patient and from source organism from patient and

from source



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TABLE 54.2 Comparison of Guidelines and Standards Pertinent to Indoor Environmentsa

Canadian WHO/Europe NAAQS/EPA SMAC NIOSH REL OSH

(ref. C-23) (ref. C-27) (ref. C-9) (ref. C-30) (ref. C-29) (ref.

Formaldehyde 0.1 ppm [L] 0.081 ppm [30 m] 0.016 ppm 0.75 p0.05 ppm [L]

b0.1 ppm [15 m] 2 ppm

Carbon dioxide 3,500 ppm [L] 5,000 ppm 10,0030,000 ppm [15 m] 30,00

Carbon monoxide 11 ppm [8 h] 87 ppm [15 m] 9 ppmg 50 ppm 35 pp25 ppm [1 h] 52 ppm [30 m] 35 ppm [1 h]

g200 ppm [C] 200 p

26 ppm [1 h] 1500 [C]8.7 ppm [8 h]

Nitrogen dioxide 0.05 ppm 0.2 ppm [1 h] 0.05 ppm [1 y] 1 ppm [15 m] 1 ppm0.25 ppm [1 h] 0.08 ppm [24 h]

Ozone 0.12 ppm [1 h] 0.080.1 ppm [1 h] 0.12 ppm [1 h] 0.1 ppm [C] 0.1 pp0.050.06 ppm [8 h] 0.08 ppm [8 h] 0.3 pp

Particlese

0.1 mg/m3 [1 h] 5 mg/m3 3 mg/

2.5 MMADd 0.040 mg/m3 [L]

Particlese

0.05 mg/m3 [1 y]

10 MMADd 0.15 mg/m3 [24 h]g

Total particlese

15g

Sulfur dioxide 0.38 ppm [5 m] 0.19 ppm [10 m] 0.03 ppm [1 y] 2 ppm 2 ppm0.019 ppm 0.13 ppm [1 h] 0.14 ppm [24 h]

g5 ppm [15 m] 5 ppm

Lead Minimize exposure 0.51.0g/m3 [1 y] 1.5 g/m3 [3 months] 0.1 mg/m3 [10 h] 0.05 m

Radon 2.7 pCi/L [1 y] 4 pCi/L [L]f

This table was prepared with Hal Levin for an appendix of Standard 62 (Ventilation for Acceptable Air Quality) and Guideline P

process at the American Society of Heating, Refrigerating and Air-Conditioning Engineers.

[ ] Numbers in brackets refer to either a ceiling or to averaging times of less than or greater to 8 hours (m minutes, h hours, y y

ified, the averaging time is 8 hours.aThe values summarized in this table include the following:

Copyright 2001 by The McGraw-Hill Companies Retrieved from: www


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has led to the need to review building plans, initial design and construction logs, commis-sioning strategies, operations and maintenance logs, and renovation work in an attempt toidentify likely sources associated with the outcome of concern.

Linkage

Linkage between diseases and exposures may occur on the basis of three theoretical con-siderations (Brennan 1987). The presence of all three is most convincing, but lesser evi-dence suffices for most purposes.

Epidemiology. Epidemiologic linkage criteria are widely recognized (Bradford Hill1965). Nevertheless, they presuppose that adequate numbers of epidemiologic investiga-tions have been completed, using the outcome of interest as an endpoint, and that these

measured the pertinent exposures. Such epidemiologic evidence exists to support the asso-ciation of nonspecific symptoms such as headaches or mucosal irritation with large officebuildings or with formaldehyde offgassing from ureaformaldehyde foam insulation. It gen-erally does not support more serious conditions such as asthma or hypersensitivity pneu-monitis.

Toxicology. Linkage based on toxicologic considerations assumes the presence ofresearch generally conducted on animals, usually with markers of exposure and effect.Most toxicologic documentation relies on some marker of exposure or effect, validated onan individual level, which exists only for infectious disease, carbon monoxide, and some

pesticides. These allow treating physicians to document the same effects and markers inhumans. For some rare phenomena, such as headaches associated with carbon monoxidepoisoning, pesticide poisoning after misapplication, or hemorrhagic pneumonitis afterexposure to Stachybotrys chartarum andAspergillus versicolor, at least some mechanisticevidence exists, either in animal or in human studies. Other effects, such as formaldehydecausing irritation, are easily recognized. Still, in individual cases, linkage is difficult.

Clinical Models. Finally, in the absence of generalizable evidence, clinical findings maybe quite persuasive. The use of lung function tests to document worsening of disease in a

specific environment, such as is possible in asthma, may be quite persuasive to physicianseven though professionals from other disciplines may fail to understand the significance ofsuch results. Such approaches have been used for unusual conditions for which no otherlinkage strategies are available.

Clinical Practice: The Sentinel Events Model. A fundamental belief of practitioners ofoccupational and environmental medicine is that single cases of disease related to an expo-sure represent sentinels, markers for an exposure, an exposed group that requires follow-up, and a cause that may be remediated. The sentinel health events mode of practice isfundamental to the good practice occupational and environmental medicine. Failure to seek

further cases of disease in this setting is considered inappropriate practice.As discussed under exposure assessment, once dose-response relationships and sam-

pling strategies have been defined clearly for specific exposures, practitioners may usemeasured levels to develop knowledge of causal relationships. In the built environment,practitioners must rely on checklists, understanding of complex systems and their designand operations problems, and maintenance failures to interpret symptoms and diseases.Often, this leads to outbreak investigation approaches of screening for similar disease in apopulation, comparison of symptom or disease rates in a control population, and attemptsto approximate exposure differences or surrogates for likely mechanisms of disease.

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Management Plans

Standard medical treatment exists for many of the diseases attributed to indoor environ-ments. Infections such as tuberculosis or Legionnaires disease must be treated with antibi-otics. Asthma usually requires medical treatment with anti-inflammatory agents. Mucosal

irritation may benefit from local treatment. In parallel to medical treatment (i.e., of theaffected individual), treatment involves some considerations of exposure control, eitherthrough removal from work or through workplace intervention (Bracker 1999). Decisionsto remove individuals from further exposure are appropriate to support symptomaticimprovement, to prevent acute attacks of a disease, and to prevent long-term progressionof disease.

The medical and scientific literature suggests that the psychological components of dis-ease are as important in clinical improvement, rehabilitation, and return to work as objec-tive measures of organ function. A first major step for all health care providers is then thenegotiation with patients about disease for clinical improvement. The usual steps in a

sometimes complicated dance are as follows:

G Showing respect

G Educating the patients

G Negotiating around differing sets of beliefs

G Defining obstacles

G Agreement on a plan

In the absence of these steps it is unlikely that, at least in subjectively severe cases, patients

will improve dramatically, even if their objective evidence of disease resolves. The firststep is often simply the expression of sympathy and the willingness to listen to the patientsstory. Cutting off the story line, interrupting the patient early on, and downplaying theseverity of the problem are likely to impede a strong relationship.

After completing the more traditional medical activities (history taking, physical exam-ination, lab testing, obtaining a diagnosis), physicians must educate patients. During suchdiscussions, the knowledge of exposures, systems, dose-response relationships, causal rela-tionships, and the limits of knowledge and uncertainty must be addressed. Often patientswill have read widely and sometimes have belief systems that differ from the traditional sci-

entific approaches of physicians. When conflicts in belief systems cannot be resolved,providers and patients must negotiate a strategy to move forward despite these beliefs. Thismay identify obstacles that may be resolved in the course of discussions with otherinvolved parties.

The implementation of environmental solutions to indoor environmental problems mayrequire participation of additional parties: landlords, building owners or managers, mainte-nance contractors, cleaning personnel, school boards, and other groups with little familiar-ity with health considerations. Each of these may have a personal and differing set of beliefsthat requires a process similar to the one outlined above. Developing a management planrequires disseminating information appropriately, developing consensus (or defining the

level by which a solution may be forced), and documenting the benefits of solutions.In general, communication strategies that avoid laying blame, that offer solutions, and

that suggest mutual ownership of the problem are most helpful. Obtaining as much cer-tainty about the actual cause of disease as possible, for example through dynamic physio-logic testing, allows health professionals far greater certainty in their initial contacts withemployers, building owners, and other nonmedical personnel. Such greater certaintyappears to be associated with the greater likelihood of persuading those parties of the sever-ity of the problem, of the credibility of the professionals involved, and of the likelihood ofsuccessful intervention.




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54.2 LUNG DISEASE TESTING

Several tests may be used for lung disease. These include spirometry, which measures theamount of air exhaled in timed volumes. Forced vital capacity (FVC) is the total amount ofair breathed out, and forced expiratory volume in the first second (FEV

1

) is the timed vol-ume after 1 second. Their ratio (FEV1/FVC ratio) represents a better indicator of airwaysobstruction (asthma, chronic obstructive pulmonary disease), that is, blockage in breathingout, than the FEV1 alone. A flow-volume loop measures forced in- and expiratory maneu-vers and can distinguish an obstruction in the chest (e.g., asthma) from upper airwaysobstruction (e.g., laryngeal spasm associated with hoarseness and laryngitis).

Lung diffusing capacity (DLCO), measured in several different ways, can document thedecreased ability of the circulation to transport oxygen efficiently and is most commonlyused as an indicator of oxygen diffusion across the lungs. Static lung volumes, total lungcapacity (TLC), and functional residual capacity (FRC) are taken as evidence of reduction

in the amount of air in the lung, as occurs in diffuse inflammation and stiffening of the lungtissues.

Measured values are compared with a set of normal values, obtained from large groupsof individuals (of which there are approximately 20 different sets), taking into account gen-der, age, height, and, sometimes, ethnic derivation because of anthropomorphometric dif-ferences. For all of these, common clinical usage holds that results of less than 80 percentof that predicted represent likely clinical abnormalities. As results approach 70 percent ofthat predicted, that certainty grows. Decreases in FVC, DLCO, TLC, and FRC are used asindicators of the restrictive lung disorders; decreases in FEV1 with a preserved FVC orFEV

1

/FVC ratios are taken as evidence of obstructive disease.Dynamic comparison of such tests may be undertaken in the laboratory or in the field.

Provocation with nonspecific irritants, such as methacholine, may document airwayshyperreactivity (twitchiness), usually considered evidence of asthma. Specific provocationwith immunologically active agents, such as bioaerosols, may be used to document asthmaor hypersensitivity pneumonitis, although such undertakings are often quite expensive.This assumes one has identified the correct antigens. Similarly, evaluation of lung functionbefore and after exposures at work, whether on a single day, single week, or several weeks,is useful to document associations when no specific agent has been identified, purified, andcharacterized.

54.3 INTERSTITIAL LUNG DISORDERS

The interstitial lung diseases (ILDs) occur at a prevalence rate of about 70 per 1,000,000persons and an incidence of 30/1,000,000 person years (Coultas 1994). Less than 3 percentof these represent hypersensitivity pneumonitis (HP), the disease most clearly associatedwith moisture and mold and widely acknowledged as the most likely disease to be buildingrelated when it occurs. Approximately 5 percent of these represent other work-related

ILDs, such as asbestosis and silicosis, 5 percent represent sarcoidosis, and the remaining80 percent represent diseases with recognized clinical characteristics but unknown causes.

Hypersensitivity Pneumonitis

Since the report of Fink (1971), hypersensitivity pneumonitis has been recognized as a con-sequence of contaminated ventilation systems. Outbreaks are associated with moisture in

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large buildings (Anonymous 1984) and with moisture in the home (Kreiss and Hodgson1984). Population-based data suggest that between 1 and 4 percent of randomly selectedoffice workers describe symptoms consistent with hypersensitivity pneumonitis, also con-sistent with organic dust toxic syndrome (ODTS, discussed later).

The disease occurs on the basis of cell-mediated immunity, although several other com-

ponents such as cytotoxicity may play a role. The disease may present in two different tem-poral patterns and varying degrees of severity. It may present acutely, with feverishness,chills, muscle aches, and chest symptoms of coughing and shortness of breath, often resem-bling an infectious pneumonia. This pattern generally leads to the recognition of a specificexposure. On the other hand, patients may present with insidious onset of fatigue and someshortness of breath without coughing.

As the disease grows more severe, patients generally feel more ill. Cases have been doc-umented with lung biopsy after patients simply felt very tired and nauseous, with chestsymptoms arising only on strenuous exercise (Rose et al. 1998). Such disease is almostalways completely reversible. On the other hand, patients may present with an acute pneu-monia requiring hospitalization in intensive care units and may undergo biopsy, docu-menting characteristic lesions. Repeated episodes, and persisting exposure, are associatedwith worse prognosis, including with long-term persisting decreases in lung function. Oncefibrosis is evident on chest x ray, full recovery is unlikely.

Differing clinical traditions held that all patients with interstitial lung disease require abiopsy, if only for the determination of prognosis, whereas others have felt comfortablewith clinical tests alone. With the spread of managed care, biopsies appear to be undertakenless frequently. This controversy has increased as more recent outbreaks have identifieddisease earlier on biopsy without any objective evidence of disease on usual clinical tests.

The usual clinical tests include spirometry, lung volumes, and lung diffusing capacityfor documentation of physiologic abnormalities; chest x rays (CXR), gallium scanning, andthin section (high resolution) computerized tomography for imaging (HRCT); and bron-chioalveolar lavage (BAL) and lung biopsies for documentation of anatomic characteris-tics and inflammatory markers. The characteristic physiologic abnormalities includedecreased FVC, DLCO, TLV, and FRC. Early on, patients may have evidence of abnormal-ities only on exercise testing (treadmill). When disease is clinically severe, almost allpatients will show abnormalities. When disease is identified early, before irreversible scar-ring has occurred, such tests are often still normal. Characteristic abnormal results on imag-ing include diffuse uptake on gallium scanning, ground glass appearance on HRCT, andalveolar and interstitial changes on CXR. HP is increasingly recognized without abnormalCXRs (Hodgson 1989, Lynch et al. 1992, Rose et al. 1998), HRCTs (Lynch et al. 1992,Rose 1998), or gallium scans (Lynch et al. 1992). Transbronchial biopsy remains the goldstandard of diagnosis, but up to 10 forceps bites may be needed for an identification rate ofover 90 percent. Antibody testing (IgG) is often undertaken but has been shown to havevery little utility (Burrell and Rylander 1981) in the diagnosis of disease although it is oftenconsidered a reasonable marker of exposure.

Diagnostic Strategies/Linkage. After an initial history and physical examination, appro-

priate tests may suggest the presence of disease. Physicians are then left with the questionof how to link disease to exposure. This often occurs through temporal linkage. A first stepmay be to evaluate individuals ability to return to work with a trial of removal and reex-posure because this may show work-related decrements. Individuals may demonstratemajor improvement in lung function even when tests are within the normal range whenexposure ceases, so following tests dynamically over time appears useful. The presence ofpotential sources at work or at home makes this more likely (Table 54.3). Some authors findantibody testing useful despite old scientific literature documenting its frequent futility.




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Prognosis and Surveillance. Often, patients have been unable to return to work (or theirhome) even after intervention that appeared successful based on disappearance of visiblebioaerosols. It remains unclear whether more rigorous cleaning would solve such problemsor whether buildings have some ecological characteristics that lead to the persistence ofantigens. Few data have attempted to follow actual exposures, symptoms, and recurrencein buildings.

At times patients have been able to return to the offending location. No long-term studiesdocument that this may occur without deleterious consequences. It is therefore worth imple-

menting a formal surveillance program in an attempt to document recurrence persistence ofrecovery. In general, symptoms are likely to recur if patients disease recurs. Greater relianceshould be placed on symptoms than on objective testing, particularly as diffusing capacitiesand lung volumes tend to be far more variable than spirometric indexes.

Long-term disability evaluation follows standard clinical practice. In general, exercisetesting is the most suitable objective test for the documentation of residual abnormalities.

Other Forms of ILD

Increasing evidence suggests that other forms of interstitial lung disease may be associatedwith work in buildings. For each there is anecdotal evidence, either in case reports or in out-breaks of disease. Only for asbestosis is there planned, generalizable research.

Asbestosis. Cases of asbestos-related interstitial lung disease (i.e., asbestosis) are associ-ated with work indoors for electricians, plumbers, carpenters, and other building trades.These exposures are no different than for similar occupations working outside of publicaccess buildings. Teachers and other building occupants, such as children, who have nosustained contact with disturbed asbestos are usually not considered at risk. Two recent

reports suggest that there may be very rare exceptions to this rule (Anderson et al. 1991,Lilienfeld 1991).The diagnosis of asbestosis is made on the basis of long-standing (i.e., usually years of

daily exposure) exposure to asbestos and evidence of interstitial lung disease on radio-graphic studies. Although lung biopsy will show characteristic asbestos bodies or providefiber counts indicating substantial exposure, these are usually considered unnecessary.

Sarcoidosis. In general, sarcoidosis is thought likely to have some identifiable etiology(Newman et al. 1996). Evidence of moisture in basements (musty odor or floods) or mold

54.12 ASSESSING IAQ

TABLE 54.3 Causes of Hypersensitivity Pneumonitis

HVAC systems

Leaf mold contaminating inlet filters

Contamination of filtersContamination of mixing plenumStanding water in drain pans with contamination

Contamination of water reservoirs used for humidification

Building envelope

Roof leaks (membranes, flashing)Below-grade moisture incursion

Wall penetration



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growing on bathroom walls is associated with sarcoidosis (Ortiz 2000). Recent reports ofHP, initially diagnosed as pulmonary sarcoidosis (Thorn 1997, Forst 1994) have suggested,as have prior studies, some difficulties distinguishing these sarcoidosis from hypersensi-tivity pneumonitis in clinical practice.

Usual Interstitial Pneumonitis. Usual interstitial pneumonitis (Mullen et al. 1998) maybe associated with moisture in basements. Additional case-control studies have suggestedthat ILDs are associated with exposure to a range of bioaerosols, including wood, grainsand hay, and farm animals (Iwai 1992, Scott 1991, Baumgartner 2000). At least one casereport of nonspecific interstitial pneumonitis, distinct from HP, associated with a myopa-thy and antibody responses similar to HP, has been attributed to Aspergillus exposure(Lonneux et al. 1995).

Organic Dust Toxic Syndrome. Some evidence exists that office workers may developyet another form of interstitial pulmonary response, possibly more frequently than com-monly assumed, called an organic dust toxic syndrome, the same disease as humidifierfever. Beginning with C. A. C. Pickerings search for humidifiers as a cause of symptomsamong office workers (Finnegan 1984), excess rates of chest tightness and flulike illnesshave been seen in buildings with humidification (Finnegan et al. 1984), HVAC systemswith water (Burge et al. 1987), and buildings with moisture problems (Sieber 1997). Datafrom a Dutch study of office workers suggested a tripling of symptom rates associatedwith a tenfold increase in airborne endotoxin concentrations (Teuuw and Vandenbroucke1994). A reanalysis of several older data sets (Apter et al. 1997) suggested that a symp-tom cluster of chest tightness, difficulty breathing, and flulike illness was distinct from

those of mucosal irritation, central nervous system symptoms, and skin irritation.Although this syndrome is considered benign and self-limited, there is some evidence forimpairment of lung function after long-term exposure or more severe illness (Milton1966, 1996, 1997).

54.4 ALLERGIC AIRWAYS AND UPPER AIRWAYS

DISEASE

Asthma

Between 5 and 8 percent of the U.S. population have asthma. In adults, about 20 per100,000 persons will develop new onset asthma from their workplace (Milton 1998) andat present approximately 15 percent of these (between 0.5 and 1 percent of the U.S pop-ulation) are thought to have occupational asthma (Venables and Chan-Yeung 1997).According to reports to the Health Departments in Michigan and Massachusetts (Kreiss1999), where occupational asthma is a reportable disease, about 20 percent of work-related asthma reported in the last years appear related to buildings relying on SENSOR

criteria (Matte et al. 1990). Only one outbreak of building-related asthma has beendescribed (Hofman et al. 1993). Jajoski et al. (1999) suggest that approximately 10 per-cent of work-related asthma reported to state departments of health in 19921993 wasattributed to office buildings. More recently, substantially greater proportions appear tobe building related (Gassert et al. 1998). Nevertheless, in support, in a recent series ofNIOSH building investigations, chest symptoms appeared related to specific aspects ofbuildings operations including moisture and dirt and debris in the ventilation system(Sieber et al. 1996). This suggests that building-related asthma may in fact be much morecommon than recognized.




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Because linkage strategies for asthma are well developed, such reports can be rigorouslyevaluated. In addition to a careful history, the primary linkage rests on documentation oftemporal relationships. Initial onset or recurrence of asthma after beginning work in abuilding, or exacerbation of previously stable asthma, may lead to suspicion of work relat-edness. Linkage relies on examination of lung function at and away from work. Although

peak expiratory flow rates are relatively easy to collect, they are often thought to produceinsensitive (high rates of false-negative tests) results. Spirometry is the preferred techniquebut is often difficult to collect because of accessibility primarily through physiciansoffices. Commercially available portable diarying spirometers have recently become avail-able and facilitate the collection of longitudinal data before, during, and after work to iden-tify patterns of exacerbation at work and improvement over weekends. Although changesof 15 percent are considered diagnostic of asthma in laboratory settings, many physicianspursue further diagnostic testing with decrements of greater than 5 percent in the course ofa day.

The standard calculations for population attributable risk (or etiologic fraction) suggestthat the population-attributable risk of asthma ranges from 13 to 26 percent for moisturein buildings, including homes and work places. Lost work time does not enter into suchcalculations. In fact, very few cases of occupational asthma related to buildings are rec-ognized as such. Nevertheless, a Swedish study of office workers (Toren et al. 1991) sug-gested that those cases die more frequently of asthma than does the general population.Premature mortality costs are also not covered in direct medical benefits. Nevertheless, afollow-up study did not confirm this elevation. That means that of the $4 billion to $6 bil-lion in annual medical costs, about $.52 billion to $1.56 billion of direct medical costs maybe related to buildings. See Chapter 4 for a more complete discussion of indoor air qual-

ity health cost.

Allergic Rhinitis

Twenty to 30 percent of the U.S. population has complaints of a stuffy or runny nose,approximately half thought to be allergic rhinitis and some proportion of these are chronicirritation. Although the disease is clearly recognizable, no good linkage strategies havebeen developed for clinical use. Such symptoms among office workers are meanwhilethought to reflect both allergy and simple mucosal irritation. Few data allow estimation ofa specific fraction due to either. Menzies et al. (1998) suggested that only 1 percent of nasalsymptoms represented an allergic response to the work environment, although in general20 to 30 percent of office workers describe regular nasal symptoms, and of these halfappear at least temporally work related (Malkin et al. 1998).

Studies of the upper respiratory tract suggest that at least some measures of effect,including cells in nasal lavage fluid, physiologic changes in the nose, and biopsy evidence(Koren et al. 1992, Ohm et al. 1993, Ohm and Juto 1993, Willes et al. 1992, Mlhave et al.1993), are present when sought with sophisticated techniques. Similarly, challenges withspecific substances are well known and widely accepted as accurate, although they are

rarely performed and not widely available clinically.Individuals with atopic rhinitis often describe mucosal irritation in the office environ-

ment. It is clear that they experience irritation at lower levels of exposure than dononatopics in controlled clinical trials (Kjaergard et al. 1985). In addition, their irritationthresholds may be substantially lower (Shusterman et al. 1998) even when they are notacutely ill. Whether this results from residual inflammation or represents some intrinsiccharacteristic of atopy remains unclear.

The direct medical costs for allergic rhinitis are estimated at $1.8 billion (Malone et al.1997). People with allergic rhinitis may lose several days of work per year or, for the period

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when they are symptomatic, have decreased productivity. Recent data suggest that at leastsome of this lost productivity may result from the choice of medications (Cockburn et al.1999). Under the assumption that half of these cases are associated with work, based onquestionnaire surveys, and under the assumption that these are associated with moistureindicators, population-attributable risks suggest an etiologic fraction of less than 6 percent

for the workplace.At present, no specific diagnostic techniques have been described to link such disease

to the workplace. It is possible to use the techniques outlined above to document changesat work, although the implementation of such studies is likely to be difficult for some tech-niques. One recent attempt to use acoustic rhinometry raised the question of allergies tocockroaches and molds being risk factors for work-related decrements in nasal function(Apter et al. 1997). Striking in that study was the rarity with which subjects who describedwork-related nasal symptoms actually described changes in nasal symptoms on a Mondayat work.

Allergic Fungal Sinusitis

Allergic fungal sinusitis is a third form of nasal disease that is at least potentially related toindoor environmental exposures. The frequency is at present unclear. Diagnosis is madethrough documentation of mucosal thickening on CT scan or other primary diagnostic pro-cedures, the documentation of eosinophilic mucin in sinus drainage or biopsy material, andthe presence of fungal organisms in those same materials (deShazo et al. 1997). Althoughthe syndrome has been defined, no cases have been documented in the scientific literature

as occurring because of exposures in the built environment. It is unclear whether fungalspecies present in the indoor environment are more likely to cause such disease or whetherexposure in the workplace is any more likely to cause such disease than exposures else-where. The organisms associated with such disease, primarily Aspergillus species, arethought to occur more frequently where moisture problems occur indoors.

54.5 MUCOSAL IRRITATION

The presence of symptoms alone is often unpersuasive as the basis for economic decisions,both in the clinical and the regulatory setting. The term nonspecific symptoms has been used torefer to such symptoms, implying the lack of specific mechanisms. This fails to acknowledgethe distinction between irritant and allergically induced symptoms. In clinical settings, mark-ers used in the diagnosis of mucosal irritation include decreased tear film break-up time, as anindicators of dry eyes, and punctate conjunctivitis, documented with lissamine green or fluo-rescein staining. In addition, in epidemiologic studies, fat foam thickness or canthal foam rep-resent markers of susceptibility, markers of chronic effects, or mechanisms of disease thatremain unclear. If these markers do not represent acute effects, they cannot be used in clinical

linkage strategies. Punctate conjunctivitis, documented with lissamine green or fluoresceinstaining, represents an acute effect. Irritation is discussed in Chaps. 17, 25, and 26.

Eye irritation is a common complaint among office workers and is thought to be bysome the primary driver for interest in office worker complaints. The studies on mucosalirritation over the last 15 years by two groups of investigators are meanwhile well known.

The work by Cain and colleagues (Cain 1996) has documented the predictable effectsof volatile organic compounds on the irritant receptor in the eyes and nose. Complex mix-tures of such agents are likely to cause more symptoms than are individual agents at lowlevels. Quantitative structure activity relationships suggest a predictable, dose-dependent




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effect (Abraham 1996), at least for nonreactive, or relatively inert, compounds. This sug-gests that mucosal symptoms among office workers may represent simple irritation bycommonly encountered volatile organic compounds.

Work by Franck, Kjaergard, Skov, and Mlhave (Kjaergard 1992) suggests that com-plaints of eye irritation are measured reliably by different questionnaires, that there are phys-

iologic indicators of eye irritation, and that at the very least subjects with those markers are atgreater risk of eye irritation than subjects without. A primary hypothesis of this group ofinvestigators is that volatile organic compounds indoors may change the physical character-istics of tear fluid and allow irritants to reach the mucosal surface in greater concentrations.See Chaps. 17 and 25.

The work by Cain and colleagues (Cain 1996) has shed more light on the considerationthat mucosal symptoms may represent simple irritation by commonly encountered volatileorganic compounds. Individual agents are therefore clearly shown to have an irritantthreshold, usually two to four orders of magnitude below established criteria such asPermissible Exposure Levels (PELs) set by the Occupational Safety and HealthAdministration, the American Conference of Governmental Industrial Hygienists, or otherstandard setting bodies. (See Chap. 20.)

Diagnostic steps may include examination of the eyes using a slit lamp and the instilla-tion of staining materials to determine dry eyes and punctate conjunctivitis. Limited clinicalinterventions are possible. A first important step is the explanation of the mechanism bywhich such symptoms arise. Second, the use of artificial tears often provides symptomaticrelief. Finally, some limited evidence suggests that better cleaning, with lowering of parti-cle levels, and humidification, especially where humidity levels are below 30 percent, maybe helpful. Where bioaerosol contamination has been identified, remediation is appropriate.

54.6 HEADACHE

Headaches are a common complaint among office workers, often associated with subjectiveloss of productivity (Schwartz et al. 1997, 1998). Although attribution to buildings is a com-mon approach, it is generally not a successful intervention for individuals, and a substantialproportion of headaches are attributed to the indoor environment without adequate charac-terization. Formal diagnostic approaches exist to identify the causes of headaches (ISSH1993). Possible indoor environmental triggers and subsequent attribution to specific sourcesmay lead to specific recommendations. On the other hand, identification of nonwork-relatedfactors and appropriate interventions are equally important. Because headaches representsuch a frequent cause of decreased work productivity, some employers have implementedworkplace headache programs with some success (Schneider et al. 1999).

54.7 INFECTIONS

Much interest in infections indoors has developed because of concerns that these might betransmitted through ventilation systems. These include human-source infections, such astuberculosis, pneumococcal pneumonias, and viruses; infections emanating from buildingsystems, such as Legionnaires disease from cooling towers or potable water systems; andinfections from other sources such as animal research facilities.

Outbreaks of tuberculosis in hospital settings are well known. Such ventilation-system-associated clusters have also been reported for office workers (Nardell et al. 1991) andattributed to dysfunctional ventilation systems in jails (Steenland 1997, Cooper-Arnold et

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al. 1999). Outbreaks of animal-source diseases, such as Q-fever or histoplasmosis frompigeon droppings, have been attributed to entrainment into ventilation systems (Kreiss andHodgson 1984). At least one outbreak of pneumococcal pneumonia has been attributed tocrowding in jails (Hoge et al. 1994), although this was thought due to person-to-persontransmission. Similarly, viral epidemics of highly contagious agents such as chicken pox

and measles have occurred through dissemination through ventilation systems.More interest has arisen recently about whether common respiratory tract viruses, pri-

marily rhinoviruses, are likely to cause excess preventable respiratory tract disease amongoffice workers that may be reduced by changes in ventilation rates (Fisk and Rosenfeld1997), although they do not distinguish between the viruses that may and those that maynot be transmitted through droplet aerosols. Older literature supported hand-to-handtransmission through secretions and suggested both experimentally and in-field studies thatthis was a more effective form of transmission than the airborne route (Gwaltney 1988,1989). At the same time, experimental evidence suggested that droplet transmission mightin fact contribute to the burden of disease (Dick et al. 1987). Because of the known associ-ations with emotional states and fomite transmission, the importance of this mode A fieldstudy in barracks appeared to support this hypothesis although no data on ventilation or airexchange rates was available (Brundage et al. 1988). Even if disease is transmitted throughdroplets, reduction in frequency through general dilution ventilation may not come cheaplybecause of the inefficiency of general dilution ventilation in reducing local exposures(Nardell et al. 1991), nor may it intervene on the disease burden associated with emotionalstates.

54.8 DERMATITIS

Contact is recognized as a common problem among office workers. This ranges from aller-gic contact urticaria, sometimes with asthma (Marx 1981, 1984), to skin irritation from dry-ness. A recent review suggests, nevertheless, that most of these symptoms actuallyrepresent simple mucosal irritation rather than allergy. Rare cases of vasculitis (palpablepurpura) have been associated with photoactive copy paper (Tencati 1983).

Recent interest has focused on whether low relative humidity is associated either withirritation alone or in combination with irritant exposures, such as volatile organic com-pounds. Close scrutiny of chamber studies shows that they clearly document mucosal irri-tation at levels below 20 percent (Andersen 1974). More recently, field studies havesuggested that mucosal irritation increases as relative humidity drops below 35 percent(Nordstrom 1994).

54.9 MISCELLANEOUS DISORDERS

The built environment is put to many uses, so it is impossible to predict all of the potentialexposures and diseases that may occur. Mixed-use buildings are those with work processesthat are not just restricted to traditional office work. Printing shops, auto body shops, anddry-cleaning establishments may contribute to the levels of volatile organic compounds inoffices. Garages, loading docks, and fossil-fuel-powered floor buffers may contribute tocarbon monoxide levels.

Other processes indoors may lead to problems. Organophosphate poisoning has beenattributed to entrained organophosphates (Hodgson 1987); such events may be more fre-quent than commonly assumed (Muldoon 1993). Emissions from architectural blueprint




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machines have been associated with palpable purpura, a form of blood vessel allergy(Tencati 1981). Carbonless copy paper has been associated with contact urticaria andasthma (Marx 1986), although the majority of complaints attributed to this exposure areconsidered to represent simple mucosal irritation (NIOSH 1999).

Equally important, physical conditions indoors may lead to comfort problems. The

combination of high indoor temperatures and low water consumption among teachers hasbeen associated with mild heat illness presenting as headaches and fatigue. Transmittedvibration from mechanical building systems has been associated with headaches, dizziness,and irritability (Hodgson 1987).

When strong suspicion arises about potential building relatedness of complaints, verythoughtful approaches may be required to identify true causal connections.

Work Stress

Consistently, in cross-sectional studies, measures of work stress are associated with indoorenvironmental symptoms (Mendell 1993). This is true whether questionnaires simply askedratings of work stressfulness or used formal validated work stress questionnaires. The scien-tific community generally agrees that work stress must be viewed as an effect modifier. Thatis, it may make the perception of irritation worse, but it will not lead to the perception of irri-tation without the presence of irritants. This does stand in contrast to some work in experi-mental psychology that suggests symptoms may arise without underlying causes but simplyfrom expectation. In a case-control study, Eriksson (1996) suggested that control over workwas the single most important factor. In any case, work stress is amenable to intervention.

Two component models of work stress argue that only job demands and the control overwork are important in workers perception of stress. Three component models include per-sonality style and characteristics as components. The first implies an organizational analy-sis and identification of possible intervention strategies focused solely on the workplacefactor. This would imply the need for management training in better supervisory practices.The second argues for the importance of scrutiny of the individual person, the environment,and the fit of the two. Solutions would then include focusing on the individual, includingreeducation, personal stress management techniques, and coping skills. A more sophisti-cated view of work stress that argues that educating both workers and management aboutbuilding needs and appropriate behaviors is appropriate risk communication, stress man-agement, and good worker education practice. Such education could then focus on man-agement and worker styles, address the recognized limitations of the current complexsystems in the office, and lead to changed expectations. See Chap. 55 for more detail.

A lesson may also be learned from the world of hazardous waste sites, community out-rage, and public health. The needs of communities, their perception of pollutedness, andtheir intellectual dependency on regulatory agencies, outside exports, the media, and otherforces beyond their control lead to major distress on their part. Over the last several years,a set of guidelines has evolved to help such communities recover. These include listeningto the concerns of the affected individuals, respecting their sense of priorities and impor-

tance, and developing agendas that respect both the publics and professionals perceptionsof needed action.

54.10 THE RESIDENTIAL ENVIRONMENT

The residential environment poses a broad set of hazards to adults and children, rangingfrom safety hazards with resulting injuries through planned emissions of pollutants, such

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as oxides of nitrogen and carbon monoxide from cooking and heating appliances throughproblems generated in construction, operations, and maintenance of homes. Over the last10 years, the residential environment has been recognized as a contributor to two primaryhealth effects that are directly attributable to the home, distinct from the injuries and acutepesticide poisoning associated with homes. These conditions include respiratory tract dis-

ease associated with moisture and bioaerosols and carbon monoxide poisoning.This chapter will not deal with the more recent literature on combustion products and

childrens asthma, including oxides of nitrogen. Nevertheless, the use of unvented spaceheaters appears to pose a similar risk for asthma. The literature on environmental tobaccosmoke and asthma will not be recapitulated.

Beginning in 1988, Strachan suggested that home dampness is associated with respira-tory tract symptoms. After an initial review of published studies in 1991 (Spengler 1992)suggesting a consistent though small increase, subsequent reviews (Cooper-Arnold 1997)have suggested that this effect is consistent. Dales et al. (1998) have recently identified notonly respiratory tract symptoms but also white cell activation. Measures of association arestronger in studies with better measures of exposure. It remains unclear whether this effectis mediated solely through known antigens, such as dust mites, fungal allergens such as

Aspergillus and Penicillium, or also from nonspecific bioaerosol mass. The prevalence ofmoisture problems is controversial, although some groups have identified a substantialnumber of houses as potential contributors to disease (Nevalainen et al. 1998). Lawton etal. (1998) have suggested that moisture flow through houses is the single best predictor ofthe total bioaerosol load. A recent Institute of Medicine publication emphasizes the impor-tance of moisture and the building envelope for at least childrens asthma.

Residential carbon monoxide poisoning has become common. Series of investigations

suggest that problems arise from improper venting of fossil fuel appliances or from entrain-ment of carbon monoxide. Retrofitting homes with increased insulation, such as throughthe use of plastic sheathing over windows, construction of basement enclosures around fur-naces and boilers, and simply increased envelope tightness (Pandian et al. 1993, Conibearet al. 1996) may contribute to the problem. Entrainment has been attributed primarily togarages and migration through doors and from the use of charcoal grills (Liu et al. 1992).A final important cause is the use of small appliances in enclosed space. Even the use ofadequate ventilation according to manufacturers recommendations may be inadequateto prevent CO poisoning. A recent study (Earnest et al. 1997) documented that air exchangerates are simply inadequate indoors even with dedicated ventilation.

54.11 CONCLUSIONS

Buildings provide shelter from the elements. Nevertheless, inadequate attention to buildingsystems, in their design, operation, and maintenance, may induce a broad range of diseases.Many of these are widely recognized as diseases but often not clearly attributed to the truesource, so disease progresses. Only cooperation between engineers, industrial hygienists,

and health care providers allows the identification and remediation of problems and themaintenance of a healthy environment.

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54. Building-Related Disease