The quality of indoor air is an ongoing public health concern, especially in the wake of evidence from numerous epidemiologic studies linking symptoms with damp homes and exposure to indoor molds.1-8 Extensive media coverage of these problems and the current obsession with "tight" energy-efficient homes have further fueled interest in indoor mold-related disease (IMRD).
Each year, a significant number of patients present to their physicians with symptoms suggesting exposure to indoor molds. Yet the diagnosis of IMRD remains difficult to confirm. A major obstacle to diagnosis is the inability to standardize indoor mold testing.9 However, other obstacles can be overcome by maintaining both a high index of suspicion and an up-to-date knowledge of the underlying mechanisms and symptoms of IMRD.
In this article, we will summarize the health effects of exposure to indoor mold and will present our approach to the workup. We will limit our discussion to respiratory problems, which are the most common manifestation of IMRD.
HEALTH EFFECTS OF INDOOR MOLD
The health effects of exposure to indoor molds can be divided into 6 categories: irritant effects, nonspecific respiratory symptoms, allergic sensitization, infection, mycotoxicosis, and psychogenic reactions.While certain fungi, such as Alternaria, Aspergillus, and Cladosporium species, are more allergenic than others, approximately 80 species are known to be allergenic.
Indoor fungal contamination can cause transient irritation of the respiratory and ocular mucosa. Symptoms may include tearing, conjunctivitis, rhinitis and, rarely, wheezing.9 A number of different fungal elements, such as glucans, proteases, ergosterol, and volatile organic compounds, may cause these symptoms.10
Glucans are a particularly important potential irritant. These cell wall constituents have inflammatory and adjuvant properties, perhaps as a result of their ability to stimulate the release of interleukin 1 and 2.10 Airway exposure to (1,3) ß-d-glucans has been associated with airway inflammation.10 However, there is a paucity of data on the presence of these fungal elements as well as other fungal products in homes, even in association with mold contamination.
It is important to remember that irritational symptoms are transient and temporally related to exposure to mold-contaminated buildings. Symptoms that persist when the person is outside the building for a prolonged period should not be attributed to "aeroirritation." It is highly doubtful that this mechanism plays a substantial role in causing respiratory symptoms, except in the most contaminated dwellings, such as those with overt flooding or other significant incursion of water. Further research is necessary to validate aeroirritation as a commonly accepted mechanism of IMRD.
Nonspecific respiratory symptoms
Several epidemiologic studies have demonstrated an association between indoor dampness/humidity and a variety of nonspecific respiratory complaints, especially in children.1-8 Typical manifestations include nasal symptoms, phlegm production, cough, wheeze, recurrent respiratory infections, fatigue, and headache.1-8
While the association between damp indoor environments and respiratory problems is well documented, there is insufficient evidence of a causal relationship.11 Several factors contribute to this, including the inability to segregate fungal from other important indoor allergens, the difficulty of measuring mold levels in house dust and other airborne specimens, and the inability to separate the irritative effects of the (1,3) ß-d-glucans and volatile organic compounds emitted by mold from other indoor irritants (such as tobacco smoke).
Allergic sensitization and hypersensitivity
Common allergic responses to indoor molds are characterized as either an IgE-mediated immediate hypersensitivity or a humoral and cell-mediated hypersensitivity pneumonitis.
Immediate hypersensitivity: This can trigger symptoms of asthma or allergic rhinitis, including rhinorrhea, nasal congestion, conjunctivitis, and wheezing. Persons with mold allergies typically are sensitive to other seasonal and perennial allergens. Indoor exposure to mold, especially at high concentrations, can play a significant role in their symptoms.
Hypersensitivity pneumonitis: The interaction between activated T cells and inhalational exposure to mold proteins can result in hypersensitivity pneumonitis. Symptoms include the common triad of cough, dyspnea, and fever. Because very high levels of airborne antigen are needed to cause hypersensitivity pneumonitis, most cases occur in occupational settings, such as those of pigeon breeders or grain farmers.12
The diagnosis of hypersensitivity pneumonitis is based on the combination of symptoms, physical findings (basilar rales, for example), hypoxemia and reduced carbon monoxide-diffusing capacity on pulmonary function tests, pulmonary infiltrates (documented by chest imaging), the presence of serum-specific IgG antibody, and a temporal association with exposure to a known triggering antigen.
Other hypersensitivity reactions: Occasionally, fungi can cause allergic fungal sinusitis (AFS) or aller-gic bronchopulmonary aspergillosis (ABPA). These are IgE-mediated illnesses characterized by fungal growth in the airway. Atopic persons are most at risk. ABPA causes bronchial inflammation, with wheeze, productive cough, fever, weight loss, and pulmonary infiltrates. AFS is a similar process that is characterized by recurrent rhinosinusitis and nasal polyps.
Indoor mold exposures are generally not considered risk factors for mycosis, especially in persons who are immunocompetent. Infections caused by fungi such as Histoplasma capsulatum and Coccidioides immitis are primarily outdoor phenomena. This is also true of Cryptococcus neoformans.
Mycotoxins are natural environmental contaminants produced by fungi. There are more than 400 known mycotoxins, which are produced by at least 350 fungi worldwide. The effects of these toxins in humans primarily result from ingestion of contaminated moldy foods, causing predominantly GI symptoms.13-15
Several recent studies have attempted to link inhalation of indoor mycotoxins with a poorly defined symptom complex that can involve practically any organ system.16-18 The pathophysiologic mechanisms underlying this "toxic mold syndrome" (TMS) are unknown.19-26 A recent review of 50 patients showed that most had other disorders that could account for their TMS-like symptoms.27 Nonetheless, this patient population tends to believe strongly that fungi are responsible for their symptoms.
Patients who believe their symptoms are related to mold exposure may be especially concerned about their health. Strong belief systems linking subjective symptoms to poor air quality can become deeply entrenched and lead to somatization in some patients.
Most mold-related illnesses are related to outdoor exposures, and IMRD is considered to be a diagnosis of exclusion. Therefore, a primary goal of the evaluation is to identify any established disorders that can masquerade as IMRD. Six general groups of disorders have been identified in patients who present with building-related symptoms (Table 1).27
A systematic approach to the workup of suspected IMRD can help avoid 3 common pitfalls:
Failure to recognize or uncover a preexisting medical disorder that could be responsible for symptoms.
Failure to diagnose an underlying condition of recent onset masquerading as IMRD.
Physician support of patient claims in the absence of credible scientific substantiation.
When a patient presents with respiratory symptoms in an area in which indoor mold illnesses are prevalent, it is reasonable to immediately start evaluating for IMRD. If there is a low probability that symptoms are mold-related, we consider it equally reasonable to investigate or empirically treat the more probable disease(s). If the diagnosis remains unclear, evaluate for IMRD.
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