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Building Related Illnesses

PCCSU Volume 25, Lesson 15


The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. The program provides information on pulmonary, critical care, and sleep medicine issues. CME is no longer available for the PCCSU program.


  • Update your knowledge and understanding of pulmonary medicine topics.
  • Update your knowledge and understanding of critical care medicine topics.
  • Update your knowledge and understanding of sleep medicine topics.
  • Learn clinically useful practice procedures.

CME Availability

Effective July 1, 2013, PCCSU Volume 25 is available for review purposes only.

Effective December 31, 2012, PCCSU Volume 24 is available for review purposes only.

Effective December 31, 2011, PCCU Volume 23 is available for review purposes only. CME credit for this volume is no longer being offered

Effective December 31, 2010, PCCU Volume 22 is available for review purposes only. CME credit for this volume is no longer being offered.

Accreditation Statement

The American College of Chest Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Statement

Credit no longer available as of July 1, 2013.

Disclosure Statement

The American College of Chest Physicians (CHEST) remains strongly committed to providing the best available evidence-based clinical information to participants of this educational activity and requires an open disclosure of any potential conflict of interest identified by our faculty members. It is not the intent of CHEST to eliminate all situations of potential conflict of interest, but rather to enable those who are working with CHEST to recognize situations that may be subject to question by others. All disclosed conflicts of interest are reviewed by the educational activity course director/chair, the Education Committee, or the Conflict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The CHEST educational standards pertaining to conflict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all CHEST CME activities are ensured of independent, objective, scientifically balanced presentations of information. Disclosure of any or no relationships will be made available for all educational activities.

CME Availability

Volume 25 Through June 30, 2013
Volume 24 Through December 31, 2012
Volume 23 Through December 31, 2011
Volume 22 Through December 31, 2010

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PCCSU Volume 25 Editorial Board

Steven A. Sahn, MD, FCCP

Director, Division of Pulmonary and Critical Care Medicine, Allergy, and Clinical Immunology
Medical University of South Carolina
Charleston, SC

Dr. Sahn has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Deputy Editor
Richard A. Matthay, MD, FCCP

Professor of Medicine
Section of Pulmonary and Critical Care Medicine
Yale University School of Medicine
New Haven, CT

Dr. Matthay has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Alejandro C. Arroliga, MD, FCCP
Professor of Medicine
Texas A&M Health Science Center
College of Medicine
Temple, TX

Dr. Arroliga has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Paul D. Blanc, MD, FCCP
Professor of Medicine
University of California, San Francisco
San Francisco, CA

Dr. Blanc has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health, Flight Attendants Medical Research Institute – university grant monies
University of California San Francisco, US Environmental Protection Agency, California Environmental Protection Agency Air Resources Board – consultant fee
Habonim-Dror Foundation Board of Trustees – fiduciary position

Guillermo A. do Pico, MD, FCCP
Professor of Medicine
University of Wisconsin Medical School
Madison, WI

Dr. do Pico has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Ware G. Kuschner, MD, FCCP
Associate Professor of Medicine
Stanford University School of Medicine
Palo Alto, CA

Dr. Kuschner has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Teofilo Lee-Chiong, MD, FCCP
Associate Professor of Medicine
National Jewish Medical Center
Denver, CO

Dr. Lee-Chiong has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health – grant monies (from sources other than industry)
Covidien, Respironics, Inc. – grant monies (from industry-related sources)
Elsevier – consultant fee

Margaret Pisani, MD, MPH, FCCP
Assistant Professor of Medicine
Yale University School of Medicine
New Haven, CT

Dr. Pisani has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Stephen I. Rennard, MD, FCCP
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

Dr. Rennard has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

AstraZeneca, Biomark, Centocor, Novartis – grant monies (from industry-related sources)

Almirall, Aradigm, AstraZeneca, Boehringer Ingelheim, Defined Health, Dey Pharma, Eaton Associates, GlaxoSmithKline, Medacrop, Mpex, Novartis, Nycomed, Otsuka, Pfizer, Pulmatrix, Theravance, United Biosource, Uptake Medical, VantagePoint – consultant fee/advisory committee

AstraZeneca, Network for Continuing Medical Education, Novartis, Pfizer, SOMA – speaker bureau

Ex Officio
Gary R. Epler, MD, FCCP

Clinical Associate Professor of Medicine
Harvard Medical School
Brigham & Women's Hospital
Boston, MA

Dr. Epler has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Lilly Rodriguez
ACCP Staff Liaison

By Daniel A. Gerardi, MD, FCCP

Dr. Gerardi is Director, Occupational Lung Disease, Saint Francis Hospital and Medical Center, Hartford, Connecticut; and Assistant Professor of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut.

Dr. Gerardi has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within this chapter.


  1. Describe the contents and health effects of indoor air.
  2. Review allergens encountered in the indoor environment.
  3. Understand specific building-related illnesses.
  4. Describe the nonspecific building-related illness.
  5. Understand the approach to a patient with suspected building-related illness.

Key words: air pollution; building-related illness; indoor air; sick-building syndrome

Abbreviations: ETS = environmental tobacco smoke; PM = particulate matter; VOC = volatile organic compound


Building-related respiratory illnesses are a heterogeneous group of disorders whose symptoms are attributable to exposures encountered in the indoor office environment. Their potentially insidious onset and variable presentation mean these illnesses can be underappreciated and difficult to diagnose, and they often produce significant morbidity. Improved awareness of these disorders and accurate diagnosis promotes early detection and reduces the adverse impact on workers’ productivity and quality of life. This article will review hazardous exposures encountered in some indoor environments, the spectrum of building-related illnesses, and a diagnostic approach to the patient with a suspected building-related illness.

Indoor Air

Americans spend 90% of their time indoors.1 Work, leisure, and recreation have become indoor activities for many individuals. The controlled indoor environment, designed to optimize comfort and luxury and to conserve energy is generally safe. But indoor air in some settings may be contaminated with toxic pollutants, infectious agents, and irritants that can produce a variety of illnesses. The type of illness attributable to indoor air varies by the type of exposure(s) encountered and the duration and intensity of exposure. Specific illnesses, such as bronchial asthma and allergy, or a spectrum of nonspecific symptoms and conditions ranging from mild to severe may develop.

Indoor air pollution contains a vast array of potential toxicants, such as gases and particulates transmitted from outside air (especially products of combustion), various infectious agents—viral, bacterial, and mycobacterial—and organic allergens, including molds, dander, and pollens. Understanding this exposure increases our awareness of commonly encountered building-related illnesses.

Environmental tobacco smoke (ETS) is a persistent danger, containing more than 4,000 gaseous and particulate products, many of which are toxicants and some of which are carcinogens. In adults, there is a dose-response relationship between ETS exposure and the development of chronic respiratory tract disease.2 Some progress has been made in reducing ETS in corporate and government facilities, but ETS in the home continues to endanger the health of exposed residents, especially children. Children exposed to ETS have reductions in lung function over time, increased absenteeism from school, and a greater risk of developing bronchial asthma.3 Residual tobacco smoke contamination remaining after extinguishing a cigarette, thirdhand smoke, also endangers children. Resuspension of smoking-related ultrafine particulate matter occurs when toddlers disturb furniture and flooring.4 Carcinogens created from the interaction of nicotine residue and common indoor pollutants such as nitrous acid further adds to young children’s exposure burden.5

The effects of ETS and other indoor air toxicants depend on multiple factors, including toxicant dose, route of exposure, and individual susceptibility. Inhalational exposures predominate, but ingestion and dermal contact are also routes of exposure. Respiratory irritant effects are the most common form of injury, but other responses, including direct toxic effects, infection, and allergy, occur. Also, a psychological effect, aggravating an organic injury, is frequently seen.6

Other respirable indoor pollutants encountered in the indoor environment include ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), radon, and volatile organic compounds (VOCs). Ozone is formed at ground level from a complex grouping of reactions involving oxides of nitrogen, VOCs, and sunlight. Its effects vary by concentration, ventilation rate, and duration of exposure, but ozone is a potent inducer of airway inflammation. Acute exposure to ozone reduces lung function while exacerbating bronchial asthma and COPD.1,7 Indoor ozone concentrations are typically less than half of outdoor ozone levels; this limits but does not eliminate its adverse health effects. Ozone reacts with various indoor compounds found on surfaces of wood, furniture, carpets, and ventilation ducts, etc, to form potentially more harmful organic products, such as formaldehyde, benzaldehyde, and acetone.8

The effects of CO are well described. Its preferential binding to the hemoglobin molecule creates a hypoxic effect whose symptoms vary with exposure concentration and duration. Fatigue and headache from low-level exposure progress to dyspnea, loss of consciousness, or death with sufficient concentration.9

In addition to being precursors to ozone, oxides of nitrogen acutely damage respiratory epithelium because of their acidic nature. They are produced by home heating or cooling appliances. These toxic gases (nitrogen oxide or nitrogen dioxide) exacerbate bronchial asthma and can intensify reactions to inhaled allergens.10,11

Sulfur dioxide is chiefly produced by fossil fuel consumption in large power plants but may also be generated by home-heating systems. It is typically involved in a complex association of other gases and particulate matter (PM) and produces a wide array of irritant and toxic effects. Bronchoconstriction in patients with chronic lung disease occurs promptly after any degree of exposure.12 Inhalation of sulfur dioxide is also centrally implicated in studies of cardiovascular and respiratory mortality.13

VOCs are likely responsible for a variety of building-related disease.14 Aldehydes, alcohols, xylenes, hydrocarbons, and esters, among others, emanate from commonly encountered sources. Office furniture, carpets, building materials, paints, and printed material are just some of the products from which VOCs sublimate. VOCs are never alone and are often seen in multiple as a form of “chemical soup,” whose exposure is best measured as the total volatile organic compound concentration in µg/m3. They frequently produce irritating effects in the upper airway and facial mucous membranes, although because of the myriad presentations, these effects are not attributed to a single substance.1,15 Systemic effects of fatigue, altered mental status, concentration impairment, and carcinogenicity have been suggested but not proven.

PM, which is produced by combustion (via diesel engine, ETS, cooking, or heating engines) or from construction dust, is another source of outdoor air pollution that penetrates and affects the indoor environment. The airway deposition of PM is based on size, with smaller particles penetrating to an alveolar level. Rough definitions of size include coarse particles, 2.5 to 10 µm; fine particles, 0.1 to 2.5 µm; and ultrafine particles, <0.1 µm. The greatest danger of PM involves the particles’ high surface area/weight ratio, which allows dangerous adsorbed pollutants to be carried deep into the lung. PM can aggravate any chronic lung disease.16 PM released in diesel exhaust has been implicated in mortality studies as promoting myocardial ischemia and thrombosis.17

Allergy and Infection

Infectious illnesses are the most recognizable of building-related illnesses. The common viral respiratory tract infection is most typical. Influenza viruses, Legionella pneumophila, and Mycobacterium tuberculosis represent more serious disease.

The effects of mold exposure have been the subject of considerable debate and are a source of great public anxiety. Mold exposure is also the nucleus of many personal injury lawsuits. Molds are ubiquitous. The concentration of outdoor molds, such as Cladosporium and Alternaria, is primarily related to moisture levels and rainfall. Indoor mold concentrations are typically lower than outdoor concentrations. Higher-than-expected indoor levels of molds such as Penicillium or Aspergillus suggest increased growth and imply water leaks and issues of humidity, provided there is a substrate (wood, carpet, decayed vegetable products) on which mold can grow.18 Reports of mold contamination in schools, homes, offices and hospitals abound.

Molds can cause specific illnesses. IgE-mediated allergic rhinitis and allergic asthma are the most common forms of hypersensitivity. They occur in atopic individuals, who often have early-onset allergic disease to multiple antigens. Allergic bronchopulmonary aspergillosis and allergic fungal sinusitis are uncommon but defined by specific diagnostic criteria. Immunocompetent patients may acquire histoplasmosis, coccidioidomycosis, or blastomycosis. Immunocompromised patients can suffer from various fungal infections including Candida, Aspergillus, and Cryptococcus. Finally, hypersensitivity reactions to molds have been described.18 Assessment of antibody levels may support this diagnosis, but it should be emphasized that serum levels imply immunity and not necessarily disease.

Beyond allergy and asthma, there are no proven long-term ill effects from mold exposure. Molds are not dominant antigens. Fewer than 5% of all individuals show sensitivity to molds.18 As an example, years of study of “black mold,” Stachybotrys species, has failed to identify even a single case of human infection, not even in an immunocompromised host.19,20 This greenish-black saprophytic mold is found in moist areas and on cellulose-bound products, but it is not usually found alone and is uncommonly aerosolized. Even when disturbed during construction, its airborne life is brief, limiting patient exposure.21 It was initially implicated in an alveolar hemorrhage syndrome among infants in Cleveland, producing widespread public concern and prompting a warning from the American Academy of Pediatrics. After an extensive evaluation, the association between the mold and alveolar hemorrhage was later dismissed as unproven by the Centers for Disease Control and Prevention.22 The initial methodology of this and other similar evaluations into the effects of mold exposure sometimes have been flawed or premature, confounding some medical and lay press.23

Another source of concern from mold exposure has been related to mycotoxins. These secondary metabolites primarily serve to reduce competition from substrate. They are not volatile and do not produce odors, although their name implies toxicity. There remain no placebo-controlled studies revealing any direct adverse effect of mycotoxins on lung function.6 In fact, a recent review from the American College of Occupational and Environmental Medicine concluded that potential ill health effects from mycotoxins were “highly unlikely at best.”18

This same lack of effect cannot be claimed for nonmold allergens. Dust mites, domestic animal dander, cockroaches, rodents, and environmental pollens are only a few of the indoor contaminants at the root of commonly occurring disease, especially in asthmatics. The prevalence of sensitivity to dust mites and cockroaches has been reported to be as high as 61% and 41%, respectively, in asthmatics living in the inner city.24 Newer reports of unusual indoor allergens derived from ornamental plants, unusual pets (lizards), insects (silverfish), and airborne foods (lentils, chickpeas) emphasize the varied nature of indoor allergic exposure.25 Approximately 20% of our population is at risk for allergy, so the significance of indoor allergens is plain.

Specific Building-Related Illnesses

Specific building-related illnesses are diseases that have objective clinical features and measurable abnormalities seen in laboratory findings, including sputum cultures, serologic studies, and spirometry. In addition to the previously mentioned infections and allergy, hypersensitivity pneumonitis represents another specific building-related illness. Its classic constellation of symptoms (fevers, rigors, dyspnea, cough, myalgias, and arthralgias) is often present without radiographic or spirometric abnormality. Restrictive physiology suggested by pulmonary function testing and a reduced diffusing capacity of the lung for CO reflect more advanced disease with potentially life-threatening consequences. An extensive list of etiologic agents, including microbial organisms, animal and vegetable products, and chemical sensitizers, was outlined by Menzies and Bourbeau.26 Newer agents are regularly documented. Home environments can be particularly important for patients with hypersensitivity to microbial organisms in whom the presentation is often insidious.27

Currently, bronchial asthma is perhaps the most commonly described work-related illness. Up to 15% of asthma is thought to be of occupational origin.28 Symptoms of shortness of breath, dry cough, chest tightness, and wheezing develop as a result of sensitization to a specific agent or, in the case of irritant-induced asthma, acute massive inhalation. Rhinoconjunctivitis can be a deceiving initial feature, with more fulminant symptoms prominent only after sufficient latency. Given the frequency of asthma in the general population and the sensitivity of the asthmatic airway to various stimuli, it is more common for asthma to be aggravated by a workplace exposure rather than caused by it. Combination syndromes of work-aggravated and work-associated asthma can exist, further complicating diagnosis and treatment. Initially, it is most important to properly diagnose bronchial asthma, then to identify any workplace association; occupational associations should be confirmed with objective testing.

Nonspecific Building-Related Illness

Patients suffering from nonspecific building-related illness have symptoms of mucous membrane irritation in combination with more generalized symptoms, having a temporal relationship to the work environment. Fatigue, or tiredness and a dull, pressure-like headache are prominent features. Patients complain of a dry throat and a congested, stuffy nose without watery rhinitis. Eye irritation is less common. Skin rash and dryness also occur but can take longer to resolve. There are no specific laboratories or radiographic abnormalities that can be assessed.29

Previously described as the “sick building syndrome,” nonspecific building-related illness may be a more descriptive and appropriate term.26,30 It emphasizes the variable presentation of the illness and places a causative building environment in perspective. The syndrome is known to occur in buildings that appear clean or safe, while unaffected individuals are found in what are considered hazardous workplaces. The variation of air quality and other building factors within a large structure are probably responsible for this phenomenon.26

Subpopulations of patients may be susceptible to illness. Those with a history of atopy or asthma or a previous history of building-related illness are particularly at risk.31 Also, symptoms are more common in those who are stressed or have personal difficulties, which has led to the debate over a psychological etiology. There has never been evidence to suggest that building-related illness has a psychiatric origin.29 More confounding, a psychogenic response can develop in patients with a prolonged and untreated building-related illness, augmenting the physical effects.32 The issue of who is affected by a building-related illness appears to relate more to the spectrum of patient response to a different agent and to the wide range in the threshold of response, (ie, the susceptibility of a given working population). Finally, the threshold of response in a building cohort can be reduced by concomitant exposures, such as allergy or air pollution, in combination with various building factors.26

Specific building factors predispose workers to illness. Overcrowding, unclean work areas, foul odors, water damage, and clustering of electronic devices promote the perception of poor air quality, making it more likely workers will be affected. Building temperatures, particularly above 23°C, have been shown to increase symptoms.33 The association between indoor humidity and building related illness is less clear. Generally, workers do not appropriately identify abnormal levels of indoor humidity. Reducing humidity in moist environments and humidifying dry indoor air can reduce complaints but pitfalls abound, as water-congested devices form a refuge for microbes.34 Building ventilation rates are more important in preventing illness, with ventilation rates >10 L/s/person found to reduce disease to its lowest likelihood.35 The most important additional factor shown to reduce potential disease is the patient/worker’s ability to control the indoor air environment. The presence of outside air significantly reduces illness, even if that air is of poor quality, and patients must have the ability to adjust temperature, open windows, or otherwise alter their indoor environment to reduce the threshold of illness.29 Interestingly, two recent surveys have suggested that changing office environments from traditional to “green” can lead to reductions in absenteeism and lost work because of employees’ perceived improvement in health and well-being.36

Approach to the Patient With Building-Related Illness

The importance of a comprehensive medical history cannot be overemphasized in any condition, but never more so than in the setting of occupational disease. A building-related illness can present subtly and progressively with symptoms that have considerable overlap with other common disorders. Workers often dismiss ailments as minor or relate them to common illnesses such as viral infections, sinusitis, or pneumonia. The delay in symptoms for such diseases as hypersensitivity pneumonitis and bronchial asthma complicates worker histories. A group of workers may not have the advantage of being evaluated by a single occupational medicine practitioner, potentially diluting a large ill cohort.

It is crucial for physicians to maintain a suitable index of suspicion for building-related illness as there are few objective physical and laboratory data to confirm illness. Laboratory data are important because physicians are obliged to rule out other specific causes of illness. This is especially true in workers’ compensation evaluations, where it is never sufficient to surmise that a disease is work-related without excluding other causes. Peak flow testing, spirometry, chest radiographs, and allergy skin testing are among the most helpful assessments in the evaluation of an ill worker.

Workplace visits can be vital for understanding worker illnesses. A walk-through of the workplace should include an assessment of the indoor climate, including temperature, humidity, and specifics of the heating and ventilation system. Are workers able to modify their climate? Can workers open doors and windows? Is there overcrowding? Is the building well maintained? Obvious areas of danger demonstrated by poor housekeeping, water incursions, and clustering of computers or photocopiers should be noticed. Evidence of rodents, insects, or other animals and more subtle water incursions can be more elusive. Physician visits are sometimes limited by time or lack of experience. To expand the evaluation, an industrial hygienist can be involved. Local, state, or federal health agencies also provide readily accessible technical expertise and air quality assessments. Employers should welcome this involvement as it reduces the potential of injury to other workers and minimizes their potential liability. Occasionally, however, the employer adopts an adversarial stance. This should be met with resolve and reason, but not enmity. Building a case for disease, if it is present, allows the situation to eventually settle to its proper conclusion.


More than half of the workforce in industrialized nations works indoors. Indoor climate is not benign and can contain myriad potential respiratory insults. Specific building-related illnesses, such as respiratory infections, occupational asthma, and hypersensitivity pneumonitis, are well described. Nonspecific building-related illness appears to be very common, although its true frequency is masked by underreporting and misdiagnosis. The heterogeneity of its presentation suggests it is a complex disorder and is not associated with exposure to a single agent.26 It is best prevented by adequate airspace ventilation (>10 L/s/person), proper maintenance and cleaning, judicious use of building materials, and worker/employer education about potential dangers. An adequate index of suspicion by health-care providers is requisite to identify disease.


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