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The role of fungi (molds) in human disease
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The role of fungi (molds) in human disease
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Literature review current through: Nov 2017. | This topic last updated: Aug 29, 2017.

INTRODUCTION — Concerns about the effects of exposure to indoor fungi on health are increasingly raised by patients. Fungi exposure can indeed cause adverse health effects, including infections, hypersensitivity disorders, and toxic/irritant effects from their by-products. Less clearly established are a variety of constitutional symptoms resulting from indoor mold exposure, including fatigue, nausea, cognitive dysfunction, and immune dysfunction, as well as putative syndromes such as "toxic mold syndrome" and "mold-induced immune dysregulation" [1-4].

Although "molds" is not scientifically accurate, it is a commonly used term for fungi. The terms "fungi" and "molds" are used interchangeably in this topic review. DNA-based studies have led to the taxonomic classification of fungi into eight phyla [5,6]. Most genera of fungi involved in human allergic diseases belong to three phyla, which are Ascomycota, Basidiomycota, and Zygomycota [7]. Previously, most fungi involved in allergic diseases where placed in the archaic group, Deuteromycetes (Fungi imperfecti), the asexual stage of fungi.

Fungi that may be found indoors and outdoors, their proven and unproven health effects, and an approach to evaluating patients with symptoms that may be related to fungi will be discussed here.

INDOOR FUNGAL EXPOSURE — Common species of fungi that can be found in the indoor environment include Cladosporium, Alternaria, Epicoccum, Fusarium, Penicillium, Aspergillus, and others (table 1).

The presence of fungal spores indoors typically results from invasion from outdoor sources, and indoor levels of fungus generally reflect the fungal levels occurring outdoors at the same time and place [8]. Outdoor fungi can gain access to the indoors via open windows or transfer on clothing or pets [9]. However, under the right conditions of humidity and temperature and in the presence of an adequate food source, fungal spores can proliferate indoors, independent of outdoor levels.

Although culture is the commonly used method to identify a fungus in the environment, DNA sequencing is an evolving approach. Appearance of a fungus growing on surfaces is not particularly helpful for its identification. As an example, the term "toxic black mold" is applied to Stachybotrys, but other fungi produce dark pigments (melanin), and not all black molds produce mycotoxins.

Indoor levels of fungal spores are typically less than outdoor levels. In a review of the indoor ambient air of 820 residences of people with no mold-related health complaints, the average indoor levels were 1252 cfu/m3, as compared with outdoor levels of 1524 cfu/m3, sampled at the same time [10]. Thus, if an environmental analysis shows an indoor concentration of fungal spores that exceeds a simultaneously measured outdoor level, it suggests indoor fungal contamination as the source.

Visible mold growth is not a reliable indicator of microbial contamination, and home characteristics (eg, home dampness) only partially explain microbial biomarker levels. In addition, there are no established standards for safe indoor fungi levels or for levels that impart health risks. In the absence of such standards, a practical guide for interpreting reports from inspections or investigations of indoor molds has been published [11].

WHAT ARE THE KNOWN HEALTH EFFECTS FROM FUNGAL EXPOSURE? — Known health effects from fungal exposure include infection, illness from ingestion of mycotoxins, and various hypersensitivity disorders (table 2).

Infection — The majority of fungi are not pathogenic to immunocompetent humans. However, certain fungi are capable of infecting otherwise healthy individuals, including dermatophytes (Trichophyton, Epidermophyton, and Microsporum), Histoplasma, Blastomyces, Cryptococcus, Coccidioides, and Paracoccidioides. (See "Dermatophyte (tinea) infections" and "Diagnosis and treatment of disseminated histoplasmosis in HIV-uninfected patients" and "Clinical manifestations and diagnosis of blastomycosis".)

In contrast, immunocompromised individuals are at risk for opportunistic infections with fungi, such as Candida, Aspergillus, Fusarium, or Mucor. Those most often affected include patients with advanced acquired human immunodeficiency virus (HIV) syndrome, those on immunosuppressant therapy or cancer chemotherapy, neutropenic patients, or patients with poorly controlled diabetes mellitus. (See "Approach to the immunocompromised patient with fever and pulmonary infiltrates" and "Overview of prevention of opportunistic infections in HIV-infected patients" and "Overview of neutropenic fever syndromes", section on 'Fungal pathogens'.)

In the proper setting, fungi can infect nearly every organ system or can become disseminated and lead to fungal sepsis. (See "Overview of Candida infections" and "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults" and "Epidemiology and clinical manifestations of invasive aspergillosis" and "Fungal rhinosinusitis" and "Candida infections of the bladder and kidneys".)

Emerging evidence in experimental animal models suggests that fungal infection/colonization of the airways is linked to immunoglobulin E (IgE)-mediated sensitivity to fungi. Proteinases produced by fungi may play a key role, and T helper type 2 (Th2) allergic responses are necessary to clear the airway of the fungi [12,13]. While these animal studies are intriguing, much more needs to be learned about these processes in humans.

Ingestion of mycotoxins — All fungi are capable of producing toxins (mycotoxins), and more than 300 mycotoxins have been identified [14]. The process and regulation of toxin production by fungi are poorly understood and appear to depend upon a number of environmental factors (eg, substrate and moisture levels). In addition, although a toxin-producing fungus may be present in any given environment, its presence alone does not ensure that it is producing or will produce mycotoxins [15].

Most of the descriptions of mycotoxicosis in humans are derived from the ingestion of moldy foods [15]. Ingestion of rye and millet contaminated with the toxin-producing fungus, Claviceps, can lead to ergotism, which is perhaps the oldest known mycotoxicosis. Ergot is an alkaloid-containing toxin with vasoconstricting properties. Ergotism can be subdivided into convulsive (acute) and gangrenous (chronic) forms. The convulsive form is often accompanied by mania and hallucinations with seizures and death in severe cases [16]. The gangrenous form, also known as "Saint Anthony's Fire," leads to ischemia and necrosis of the extremities.

Aflatoxins, produced by Aspergillus species, are also of medical significance. Foods for consumption by humans and animal feeds are monitored for aflatoxin contamination as part of standard food safety practices in most developed countries [17], but contamination of peanut products supplied to developing nations as nutritional supplements has been reported [18,19]. In addition, chronically high dietary levels of aflatoxins have been implicated in the development of hepatocellular carcinoma. (See "Epidemiology and etiologic associations of hepatocellular carcinoma", section on 'Aflatoxin'.)

Other reports of mycotoxicosis in the literature involve ingestions of fumonisins from Fusarium, ochratoxin from Penicillium, and trichothecenes from Fusarium, Aspergillus, and Stachybotrys species [15].

Fungus balls — Fungi, particularly Aspergillus species, can colonize the paranasal sinuses, lungs, kidneys, or brain and form noninvasive collections of fungal mycelia (or fungus balls). These structures generally form in patients with underlying anatomic abnormalities or previous damage to the affected organ (eg, a pre-existing pulmonary cavitary lesion) and are treated with surgical removal. (See "Clinical manifestations and diagnosis of chronic pulmonary aspergillosis" and "Treatment of chronic pulmonary aspergillosis" and "Fungal rhinosinusitis", section on 'Fungus balls' and "Candida infections of the bladder and kidneys", section on 'Fungus balls'.)

Disorders involving hypersensitivity to fungi — The term "hypersensitivity" refers to immunologically-mediated conditions, in which the patient generates an abnormal immune response to a trigger, resulting in inflammation and symptoms. IgE-mediated allergy is one type of hypersensitivity reaction. While "allergic disease" is traditionally associated with an adaptive IgE-mediated immune response, increasing evidence suggests that the innate immune system plays an important role, as well [20,21]. Fungal products can initiate innate immune responses via their actions on pattern recognition receptors (PRRs) [22] and through pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) [23]. Type 2 innate lymphoid cells (ICL-2s) also appear to be involved in these processes [24]. Inflammation generated by these innate responses may account for a lack of correlation between the presence of IgE antibodies to fungal allergens and the presence of symptoms of allergic diseases.

There are several defined disorders that involve hypersensitivity reactions to fungi, including asthma and allergic rhinitis, hypersensitivity pneumonitis (HP), allergic bronchopulmonary aspergillosis (ABPA), and allergic fungal rhinosinusitis (AFRS).

Asthma — The role of sensitivity to fungal allergens in asthma is relatively well-established. A growing body of evidence suggests that sensitization and exposure to outdoor fungi, particularly Alternaria, are associated with asthma [25,26]. However, a direct causal relationship between outdoor fungal exposure and asthmatic symptoms has been more difficult to establish. A pediatric study revealed that asthma symptoms and need for inhaled bronchodilator therapy were correlated with the total outdoor spore count [27]. Interestingly, the spore counts of those fungi to which the children were not skin tested (Basiomycetes and Ascospores), for which skin testing reagents are not available, correlated better with symptoms than the counts of those fungi to which the children had positive skin tests (Deuteromycetes) [27]. Fungal allergy is also associated with an increased risk of life-threatening and fatal asthma [28].

Fungal exposure and sensitization appear to play an important role in lower respiratory tract disease [29]. In addition, a link between fungi and severe asthma is emerging [30]. The term "severe asthma with fungal sensitization" (SAFS) has been proposed, and a clinical trial of the oral antifungal (itraconazole) demonstrated improvement in Asthma Quality of Life Questionnaire scores in 60 percent of patients [31]. Clearly, further studies will be needed to establish this treatment for this asthma phenotype [32,33]. (See "Investigational agents for asthma", section on 'Antifungal agents'.)

Several studies suggest that exposure to indoor molds and home dampness are related to adverse respiratory health effects (particularly cough and wheezing), especially in children [34-37]. Often these studies rely on the self-reported presence of visible mold growth/dampness in the home. The potential mechanism(s) of these effects are unknown but may not involve IgE-mediated sensitization.

Findings regarding the relationship between indoor fungal exposure and asthma are conflicting. Some studies suggest that fungal exposure is a risk factor for asthma development. These include one that found that the presence of indoor visible mold growth in the homes of infants was a risk factor for a positive asthma predictive index (API) at age three years, another that found an association between airway hyper-reactivity and exposure to airborne Penicillium species in the home, and a third that found that mold problems in the kitchen and main living area increased the risk for wheezing in early childhood [38-40]. In contrast, other studies failed to find associations between various measures of indoor mold exposure and later development of wheezing or asthma in children [41,42].

Several studies have found associations between "dampness" of the indoor environment and asthma symptoms [34,35,43-46]. However, indoor dampness promotes the growth of bacteria and dust mites, in addition to fungi, and it is often difficult to determine which factor contributes most to the development of respiratory symptoms. In contrast to the above studies, investigations of settings with extensive water damage and mold growth are ongoing, but a study of American children whose homes were affected by Hurricane Katrina showed that six months after the event, the children's lung function was normal [47]. Thus, the impact of damp environments on health is not clear.

Outdoor fungal exposure may prove to be more important than indoor exposure. One prospective study found that outdoor fungal exposure, as opposed to indoor fungal exposure, was associated with asthma symptoms in inner city asthmatic children [48]. Another study identified higher exposures to outdoor fungi in the first three months of life as a risk factor for early wheezing [49].

Allergic rhinitis — It seems intuitive that IgE-mediated sensitivity to fungal allergens could be a cause of allergic rhinitis, although literature supporting this assertion is sparse. Allergic rhinitis symptoms have correlated with positive skin tests and positive in vitro tests to the common outdoor molds, Alternaria and Cladosporium.

A meta-analysis of 21 studies on rhinitis found that self-reported exposure to indoor mold odor conferred an increased risk for allergic rhinitis (relative risk [RR] 1.87, 95% CI 0.95-3.68), and similarly, the risk for allergic rhinitis was also increased with self-reported visible indoor mold growth (RR 1.51, 95% CI 1.39-1.64) [50].

An Australian study found that children with positive skin tests to Alternaria had an increase in nocturnal nasal symptoms and had eye symptoms that correlated well with the ambient air concentrations of Alternaria [51].

Another study found an increased risk of allergic sensitization with increasing viable indoor mold levels to the Aspergillus and Cladosporium, and those children exposed to the highest levels (>90th percentile) of fungi were more likely to experience allergic rhinoconjunctivitis symptoms [52].

A third study of 6726 children found that sensitization to Alternaria was associated with allergic rhinitis, independent of asthma [53].

Overall, more investigation is needed regarding the role of fungi and in particular indoor fungi, in the causation of allergic rhinitis. The evidence to support a role of sensitization to Stachybotrys chartarum in allergic rhinitis is lacking. The diagnosis and management of allergic rhinitis, from any cause, are reviewed elsewhere. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis" and "Pharmacotherapy of allergic rhinitis".)

Hypersensitivity pneumonitis — Sensitivity to fungal antigens is among the most common cause of hypersensitivity pneumonitis (HP) [54]. HP usually develops from occupational fungal exposures, although there are several reports of HP resulting from fungal contamination in the home. Fungus-contaminated showers, air conditioning systems, and humidifiers have been reported as sources of causative antigens in HP [54-57]. Species of Epicoccum, Aspergillus, Penicillium, Rhodotorula, and Aureobasidium, among others, have been implicated. (See "Epidemiology and causes of hypersensitivity pneumonitis (extrinsic allergic alveolitis)".)

Allergic bronchopulmonary aspergillosis — Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus in the lower airways, often in patients with underlying asthma or cystic fibrosis. Patients develop recurrent episodes of cough, fever, malaise, expectoration of brownish mucous plugs, and sometimes hemoptysis. ABPA is discussed in greater detail separately. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)

Allergic fungal rhinosinusitis — Allergic fungal rhinosinusitis (AFRS) patients typically present with recurrent or chronic rhinosinusitis (CRS) with nasal polyposis, which is often refractory to prolonged antibiotic therapy. Many have serum fungal-specific IgE antibodies, as well as elevated serum total IgE levels. Thick, tenacious mucus, called eosinophilic mucin, is often present in surgically-obtained specimens. To make the diagnosis, the presence of fungi must be demonstrated either histologically or with positive fungal cultures. There must be no evidence of fungal invasion of the underlying mucosa, in order to differentiate AFRS from invasive fungal sinusitis. Treatment of AFRS consists of systemic glucocorticoid treatment and surgery to remove allergic mucin, which is typically impacted and inspissated. Recurrences are common without ongoing therapy to control inflammation. The diagnosis and management of AFRS are presented separately. (See "Allergic fungal rhinosinusitis".)


Inhalation of mycotoxins and/or fungal spores — The ingestion of mycotoxins can cause disease (see 'Ingestion of mycotoxins' above). In contrast, illness resulting from the inhalation of mycotoxins has not been demonstrated. Mycotoxins are relatively large molecules, are not significantly volatile, and usually will not evaporate or "off-gas" into the environment.

Much attention on the health effects of indoor mold exposure has focused on the fungus Stachybotrys chartarum (also known as Stachybotrys atra or Stachybotrys alternans). S. chartarum is a fungus that is found worldwide. It has a high moisture requirement and grows optimally at a relative humidity of 93 percent. S. chartarum spores are relatively sticky and not easily aerosolized. The fungus is difficult to culture, as it does not grow well on standard media and does not compete well with other molds or bacteria.

S. chartarum can produce mycotoxins (macrocyclic trichothecenes), but not all strains of S. chartarum do so, and various factors including substrates on which the fungus grows and moisture levels influence mycotoxin production. The concentrations that can be generated and become airborne are controversial [1,15,58,59].

Inhalation of fungal toxins and other fungal debris can occur, but it requires the production of an aerosol that contains fungal fragments, such as in an occupational setting. The occupational disorder "pulmonary mycotoxicosis" has been described in workers exposed to large quantities of fungal material while cleaning silos and has been referred to as "silo-unloader's disease" or "grain fever syndrome." Symptoms include an influenza-like syndrome with cough, dyspnea, chest tightness, fever, chills, headache, malaise, myalgias, facial warmth, and nausea. Illness is typically self-limited, and patients recover without residual lung impairment.

The condition is more properly referred to as the organic dust toxic syndrome (ODTS), since it has never been shown that mycotoxins are responsible for the development of the disease and because the inhaled dust contains a variety of fungi, bacteria, and organic debris, including endotoxin. (See "Diagnosis of hypersensitivity pneumonitis (extrinsic allergic alveolitis)", section on 'Organic dust toxic syndrome'.)

Exposure to such significant fungal aerosols is unlikely to occur outside of the occupational setting. Reports from the American College of Environmental and Occupational Medicine and the Institute of Medicine concluded that the evidence does not support the contention that mycotoxin-related illness occurs via inhalation in nonoccupational settings, and the relationship between inhalation exposure and adverse health effects is controversial [1,15,60].

Acute idiopathic pulmonary hemorrhage — Stachybotrys received a great deal of publicity initially following a geographic cluster of eight cases of acute idiopathic pulmonary hemorrhage (AIPH) that occurred in the inner city of Cleveland, Ohio between January 1993 and November 1994. Two additional cases were identified in December 1994. Investigators sought an environmental cause, since all of the infants lived in the same area of eastern metropolitan Cleveland [61]. A case control study revealed that all 10 of the infants resided in homes with major water damage that had occurred in the previous six months and that quantitative air sampling and microscopic identification revealed higher mean colony counts of S. atra in the cases when compared with controls [62].

Because of this finding, exposure to Stachybotrys was interpreted as the probable cause of AIPH, despite the report's caution that "further efforts are needed to clarify the association between pulmonary hemorrhage and water-damaged building materials" [62]. However, subsequent review by the Centers for Disease Control (CDC) and Prevention found that the studies contained major flaws with regard to data analysis, sampling techniques, and classification of "water-damaged homes." Given these limitations, the reviewers ultimately concluded that "the studies were not of sufficient quality to support an association between S. chartarum and AIPH" [63]. Exposure to environmental tobacco smoke may be another important contributing factor in AIPH [64]. (See "Hemoptysis in children", section on 'Pulmonary parenchymal diseases'.)

Chronic rhinosinusitis — It has been proposed that fungi may be important in the pathogenesis of various forms of chronic rhinosinusitis (CRS), apart from allergic fungal rhinosinusitis (AFRS), based on the recovery of fungal organisms from sinus surgical specimens [65]. However, fungi can frequently be recovered from the nasal passages of normal individuals. Clear-cut evidence that the presence of fungi (without evidence of immunoglobulin E [IgE]-mediated allergy to fungi) causes CRS is lacking, and treatment with topical antifungals (eg, amphotericin B) has not been established as an effective therapy [66].

Other research has postulated that the protease activity of fungi may possibly play a role in the pathogenesis of CRS through non-IgE-mediated mechanisms. Specifically, protease activity of the fungus Alternaria has been shown to activate and degranulate human eosinophils, which are abundant in the mucosa of patients with chronic sinus disease [67]. In addition, fungal protease may enhance T helper type 2 (Th2)-driven (allergic) responses by acting as adjuvants that increase IgE-mediated mechanisms in animal models [68]. The role of these mechanisms in chronic sinus disease remains speculative, however. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Features of specific subtypes' and "Allergic fungal rhinosinusitis", section on 'Pathogenesis'.)

Immunologic disorders — Humans are not known to mount immunologic responses to mycotoxins as part of any disease process, and tests for antibodies to mycotoxins in human sera have not been scientifically validated [2]. There is no evidence to support a role of S. chartarum mycotoxins in the causation of immunodeficiency (also known as "mold-induced immune dysregulation") or autoimmunity [2,69].

Neurologic symptoms — The role of inhalation of either S. chartarum spores or toxins has been incriminated as the cause of neurologic symptoms. Most studies investigating neurologic disorders secondary to fungal exposure have typically described the complaints in vague terms and did not define specific neurologic deficits or use objective testing or findings to confirm the presence of neurologic dysfunction [70-72].

Irritant effects — Several fungal components and metabolites have been studied for health effects with variable results. Beta-(1,3)-D-glucans are cell wall components of fungi, plants, and bacteria. Exposure to beta-(1,3)-D-glucans has been associated with irritant effects on the upper and lower airways in some studies [73], although this has not been conclusively proven. Beta-(1,3)-D-glucans can also have immunomodulatory effects in vitro (eg, dampen Th2 responses) [74]. Hydrophobins are surface proteins produced by filamentous fungi. A hydrophobin from Cladosporium has been identified as an allergen [74], but the overall contribution of these allergens to human health has not been established.

Significant attention has been focused on volatile organic compounds (VOCs) and their role as respiratory irritants. More than 300 VOCs have been identified in the typical indoor environment, with the majority arising from building materials, combustion processes, and consumer products, such as cleaning and personal care products [75].

Fungi and other micro-organisms (eg, bacteria) are also capable of producing VOCs, such as alcohols, ketones, and aldehydes, which are released into the air [76]. These are collectively called microbial volatile organic compounds (MVOCs). MVOCs are responsible for the "musty" odor that often indicates the presence of molds [77] and are also an indicator of excessive moisture in the environment.

The odor of VOCs may be aversive to some patients and can cause symptoms in patients with underlying rhinitis or asthma, although these symptoms generally resolve within a short period of time with simple avoidance. Exposure to fungal MVOCs has been reported to cause ocular and upper airway irritation [74], although the overall significance of indoor environmental fungal VOCs on health has not been clarified.

Other disorders — There is no literature to support the role of inhalational exposure of Stachybotrys mycotoxins in spontaneous abortions [69]. Similarly, there is no evidence to implicate S. chartarum mycotoxins in malignancy, hepatobiliary disease, renal disease, or endocrine disease [2,69].

HOW DOES ONE EVALUATE THE PATIENT WITH SUSPECTED FUNGAL ASSOCIATED DISEASE? — Patients presenting with symptoms of asthma, hypersensitivity pneumonitis (HP), rhinitis, or rhinosinusitis should first be evaluated with the appropriate diagnostic tests for these disorders. A brief questionnaire may be useful in establishing an association between fungal exposure and increased symptoms (table 3) [78]. Additional testing for fungal sensitivity would be appropriate to confirm the suspected diagnosis. Once the diagnosis has been established, additional testing to determine fungal sensitivity may be appropriate in some settings:

Serum tests and/or skin testing for specific immunoglobulin E (IgE) antibodies to inhalant allergens (including fungi) are warranted in the diagnosis of allergic rhinitis and allergic asthma when there is a high suspicion of fungal exposure. Relevant species include Penicillium chrysogenum, Cladosporium species, Aspergillus fumigatus, Alternaria alternata, Candida albicans, and several others [78]. Prick skin testing was more sensitive than in vitro testing for specific IgE in one report [79]. However, the reagents used for testing are not standardized, and a combination of skin tests and specific serum IgE levels to fungi may be necessary to accurately diagnose fungal allergy [80]. This approach may be particularly important in patients with severe asthma. Cross-reactivity among fungal allergens is common [81] and is likely related to phylogenetic kinship [4,7].

Patients with symptoms of allergic bronchopulmonary aspergillosis (ABPA) should be tested for Aspergillus-specific IgE and precipitating immunoglobulin G (IgG) antibodies to Aspergillus. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)

The role of IgE and IgG antibodies to Stachybotrys in allergic disease has not been fully defined [2].

In patients suspected of having HP, assays for precipitating IgG antibodies to fungi should be obtained [2]. (See "Diagnosis of hypersensitivity pneumonitis (extrinsic allergic alveolitis)".)

Patients with recurrent respiratory infections should be evaluated with appropriate immunologic testing. Testing of parameters without known clinical utility is not validated in general and for "mold-induced immune dysregulation" specifically [2]. (See "Approach to the adult with recurrent infections" and "Approach to the child with recurrent infections" and "Laboratory evaluation of the immune system".)

The following tests are not validated for use in the diagnosis of established fungi-related disorders [82]:

Tests for the presence of mycotoxins in serum or urine

Antibodies to mycotoxins in sera

Fungus-specific immunoglobulin A (IgA) and immunoglobulin M (IgM)

Patients whose signs and symptoms do not suggest a disorder that is known to be related to fungi should be evaluated further based upon their specific complaints. As an example, patients with prominent cognitive symptoms may need neuropsychologic testing to determine if there is objective impairment. (See "Mild cognitive impairment: Epidemiology, pathology, and clinical assessment".)

Commercial home assessments — Patients who are diagnosed with a known fungus-related condition and demonstrate evidence of exposure to a specific fungus should then consider an evaluation of their home and work/school environments for growth of the implicated species. Helpful guidance for providers in determining the need for a home assessment is available [83]. In many cases, mold growth in the home can be easily detected with simple inspection and a careful review of the home for sources of dampness or standing water. Patients should understand that commercial assessments for indoor mold contamination can be costly, are not standardized, and may not discover a significant source of mold that was not already apparent. Indoor fungal levels must be compared with simultaneously collected outdoor levels. Information on an appropriate inspection and report are also available [84].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Allergic bronchopulmonary aspergillosis (The Basics)")


Some species of fungi that can be found in the indoor environment include those shown in the table (table 1). There are no established standards for safe indoor fungi levels, nor are there defined levels that are associated with illness. (See 'Indoor fungal exposure' above.)

Disorders that are attributable to fungi include various fungal infections, fungal balls, hypersensitivity reactions to fungal exposure (such as allergic asthma and rhinitis), hypersensitivity pneumonitis (HP), allergic bronchopulmonary aspergillosis (ABPA), and allergic fungal rhinosinusitis (AFRS) (table 2). (See 'What are the known health effects from fungal exposure?' above.)

The ingestion of mycotoxin-contaminated food can be a source of illness. (See 'Ingestion of mycotoxins' above.)

The inhalation of mycotoxins (eg, "toxic mold syndrome") has not been substantiated as a cause of disease. Other disorders that have not been demonstrated to be related to fungal exposure include acute idiopathic pulmonary hemorrhage (AIPH), chronic rhinosinusitis (CRS) (in the absence of fungal allergy), and various immunologic (eg, mold-induced immune dysregulation) or neurologic/cognitive signs and symptoms. (See 'What are the controversial health effects from fungal exposure?' above.)

Patients presenting with signs or symptoms attributed to fungal exposure should first be evaluated to determine what specific disorder, if any, is present. If the patient has a condition that is known to be mold-related, then selective testing to determine fungal sensitization is appropriate. It is rarely productive to start the evaluation process with a commercial home assessment for indoor fungus. (See 'How does one evaluate the patient with suspected fungal associated disease?' above.)

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  1. Committee on Damp Indoor Spaces and Health. Damp Indoor Spaces and Health, Institute of Medicine of the National Academies (Ed), The National Academies Press, Washington, DC 2004.
  2. Bush RK, Portnoy JM, Saxon A, et al. The medical effects of mold exposure. J Allergy Clin Immunol 2006; 117:326.
  3. Pettigrew HD, Selmi CF, Teuber SS, Gershwin ME. Mold and human health: separating the wheat from the chaff. Clin Rev Allergy Immunol 2010; 38:148.
  4. Baxi SN, Portnoy JM, Larenas-Linnemann D, et al. Exposure and Health Effects of Fungi on Humans. J Allergy Clin Immunol Pract 2016; 4:396.
  5. Hibbett DS, Taylor JW. Fungal systematics: is a new age of enlightenment at hand? Nat Rev Microbiol 2013; 11:129.
  6. Levetin E, Horner WE, Scott JA, Environmental Allergens Workgroup. Taxonomy of Allergenic Fungi. J Allergy Clin Immunol Pract 2016; 4:375.
  7. Soeria-Atmadja D, Onell A, Borgå A. IgE sensitization to fungi mirrors fungal phylogenetic systematics. J Allergy Clin Immunol 2010; 125:1379.
  8. Solomon WR. Assessing fungus prevalence in domestic interiors. J Allergy Clin Immunol 1975; 56:235.
  9. Bardana EJ Jr. Indoor air quality and health does fungal contamination play a significant role? Immunol Allergy Clin North Am 2003; 23:291.
  10. Gots RE, Layton NJ, Pirages SW. Indoor health: background levels of fungi. AIHA J (Fairfax, Va) 2003; 64:427.
  11. Horner WE, Barnes C, Codina R, Levetin E. Guide for interpreting reports from inspections/investigations of indoor mold. J Allergy Clin Immunol 2008; 121:592.
  12. Porter P, Susarla SC, Polikepahad S, et al. Link between allergic asthma and airway mucosal infection suggested by proteinase-secreting household fungi. Mucosal Immunol 2009; 2:504.
  13. Porter P, Polikepahad S, Qian Y, et al. Respiratory tract allergic disease and atopy: experimental evidence for a fungal infectious etiology. Med Mycol 2011; 49 Suppl 1:S158.
  14. Rylander R. Airborne (1-->3)-beta-D-glucan and airway disease in a day-care center before and after renovation. Arch Environ Health 1997; 52:281.
  15. Hardin BD, Kelman BJ, Saxon A. Adverse human health effects associated with molds in the indoor environment. J Occup Environ Med 2003; 45:470.
  16. De Costa C. St Anthony's fire and living ligatures: a short history of ergometrine. Lancet 2002; 359:1768.
  17. Cigić IK, Prosen H. An overview of conventional and emerging analytical methods for the determination of mycotoxins. Int J Mol Sci 2009; 10:62.
  18. Azziz-Baumgartner E, Lindblade K, Gieseker K, et al. Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004. Environ Health Perspect 2005; 113:1779.
  19. Paul Wild C, Montesano R. An order of Plumpy'nut, hold the aflatoxins. Science 2008; 322:1464.
  20. Williams PB, Barnes CS, Portnoy JM, Environmental Allergens Workgroup. Innate and Adaptive Immune Response to Fungal Products and Allergens. J Allergy Clin Immunol Pract 2016; 4:386.
  21. Lambrecht BN, Hammad H. Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol 2014; 134:499.
  22. Snelgrove RJ, Gregory LG, Peiró T, et al. Alternaria-derived serine protease activity drives IL-33-mediated asthma exacerbations. J Allergy Clin Immunol 2014; 134:583.
  23. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007; 81:1.
  24. Doherty TA. At the bench: understanding group 2 innate lymphoid cells in disease. J Leukoc Biol 2015; 97:455.
  25. Bush RK, Prochnau JJ. Alternaria-induced asthma. J Allergy Clin Immunol 2004; 113:227.
  26. Salo PM, Arbes SJ Jr, Sever M, et al. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol 2006; 118:892.
  27. Delfino RJ, Coate BD, Zeiger RS, et al. Daily asthma severity in relation to personal ozone exposure and outdoor fungal spores. Am J Respir Crit Care Med 1996; 154:633.
  28. Bush RK. Fungal Sensitivity: New Insights and Clinical Approaches. J Allergy Clin Immunol Pract 2016; 4:433.
  29. Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol 2012; 129:280.
  30. Denning DW, O'Driscoll BR, Hogaboam CM, et al. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J 2006; 27:615.
  31. Denning DW, O'Driscoll BR, Powell G, et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am J Respir Crit Care Med 2009; 179:11.
  32. Agarwal R, Gupta D. Severe asthma and fungi: current evidence. Med Mycol 2011; 49 Suppl 1:S150.
  33. Gore RB. The utility of antifungal agents for asthma. Curr Opin Pulm Med 2010; 16:36.
  34. Fisk WJ, Lei-Gomez Q, Mendell MJ. Meta-analyses of the associations of respiratory health effects with dampness and mold in homes. Indoor Air 2007; 17:284.
  35. Hagmolen of Ten Have W, van den Berg NJ, van der Palen J, et al. Residential exposure to mould and dampness is associated with adverse respiratory health. Clin Exp Allergy 2007; 37:1827.
  36. Mendell MJ, Mirer AG, Cheung K, et al. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence. Environ Health Perspect 2011; 119:748.
  37. Antova T, Pattenden S, Brunekreef B, et al. Exposure to indoor mould and children's respiratory health in the PATY study. J Epidemiol Community Health 2008; 62:708.
  38. Iossifova YY, Reponen T, Ryan PH, et al. Mold exposure during infancy as a predictor of potential asthma development. Ann Allergy Asthma Immunol 2009; 102:131.
  39. Bundy KW, Gent JF, Beckett W, et al. Household airborne Penicillium associated with peak expiratory flow variability in asthmatic children. Ann Allergy Asthma Immunol 2009; 103:26.
  40. Karvonen AM, Hyvärinen A, Roponen M, et al. Confirmed moisture damage at home, respiratory symptoms and atopy in early life: a birth-cohort study. Pediatrics 2009; 124:e329.
  41. Rosenbaum PF, Crawford JA, Anagnost SE, et al. Indoor airborne fungi and wheeze in the first year of life among a cohort of infants at risk for asthma. J Expo Sci Environ Epidemiol 2010; 20:503.
  42. Holme J, Hägerhed-Engman L, Mattsson J, et al. Culturable mold in indoor air and its association with moisture-related problems and asthma and allergy among Swedish children. Indoor Air 2010; 20:329.
  43. Pekkanen J, Hyvärinen A, Haverinen-Shaughnessy U, et al. Moisture damage and childhood asthma: a population-based incident case-control study. Eur Respir J 2007; 29:509.
  44. Verhoeff AP, Burge HA. Health risk assessment of fungi in home environments. Ann Allergy Asthma Immunol 1997; 78:544.
  45. Thacher JD, Gruzieva O, Pershagen G, et al. Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort. Allergy 2017; 72:967.
  46. Holst GJ, Høst A, Doekes G, et al. Allergy and respiratory health effects of dampness and dampness-related agents in schools and homes: a cross-sectional study in Danish pupils. Indoor Air 2016; 26:880.
  47. Rabito FA, Iqbal S, Kiernan MP, et al. Children's respiratory health and mold levels in New Orleans after Katrina: a preliminary look. J Allergy Clin Immunol 2008; 121:622.
  48. Pongracic JA, O'Connor GT, Muilenberg ML, et al. Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children. J Allergy Clin Immunol 2010; 125:593.
  49. Harley KG, Macher JM, Lipsett M, et al. Fungi and pollen exposure in the first months of life and risk of early childhood wheezing. Thorax 2009; 64:353.
  50. Jaakkola MS, Quansah R, Hugg TT, et al. Association of indoor dampness and molds with rhinitis risk: a systematic review and meta-analysis. J Allergy Clin Immunol 2013; 132:1099.
  51. Andersson M, Downs S, Mitakakis T, et al. Natural exposure to Alternaria spores induces allergic rhinitis symptoms in sensitized children. Pediatr Allergy Immunol 2003; 14:100.
  52. Jacob B, Ritz B, Gehring U, et al. Indoor exposure to molds and allergic sensitization. Environ Health Perspect 2002; 110:647.
  53. Randriamanantany ZA, Annesi-Maesano I, Moreau D, et al. Alternaria sensitization and allergic rhinitis with or without asthma in the French Six Cities study. Allergy 2010; 65:368.
  54. Hogan MB, Patterson R, Pore RS, et al. Basement shower hypersensitivity pneumonitis secondary to Epicoccum nigrum. Chest 1996; 110:854.
  55. Banaszak EF, Thiede WH, Fink JN. Hypersensitivity pneumonitis due to contamination of an air conditioner. N Engl J Med 1970; 283:271.
  56. Volpe BT, Sulavik SB, Tran P, Apter A. Hypersensitivity pneumonitis associated with a portable home humidifier. Conn Med 1991; 55:571.
  57. Siersted HC, Gravesen S. Extrinsic allergic alveolitis after exposure to the yeast Rhodotorula rubra. Allergy 1993; 48:298.
  58. Levy MB, Fink JN. Toxic mold syndrome. Adv Appl Microbiol 2004; 55:275.
  59. Pestka JJ, Yike I, Dearborn DG, et al. Stachybotrys chartarum, trichothecene mycotoxins, and damp building-related illness: new insights into a public health enigma. Toxicol Sci 2008; 104:4.
  60. Mazur LJ, Kim J, Committee on Environmental Health, American Academy of Pediatrics. Spectrum of noninfectious health effects from molds. Pediatrics 2006; 118:e1909.
  61. Centers for Disease Control and Prevention (CDC). Acute pulmonary hemorrhage/hemosiderosis among infants--Cleveland, January 1993-November 1994. MMWR Morb Mortal Wkly Rep 1994; 43:881.
  62. Etzel RA, Montaña E, Sorenson WG, et al. Acute pulmonary hemorrhage in infants associated with exposure to Stachybotrys atra and other fungi. Arch Pediatr Adolesc Med 1998; 152:757.
  63. Centers for Disease Control and Prevention (CDC). Update: Pulmonary hemorrhage/hemosiderosis among infants--Cleveland, Ohio, 1993-1996. MMWR Morb Mortal Wkly Rep 2000; 49:180.
  64. Dearborn DG, Smith PG, Dahms BB, et al. Clinical profile of 30 infants with acute pulmonary hemorrhage in Cleveland. Pediatrics 2002; 110:627.
  65. Taylor MJ, Ponikau JU, Sherris DA, et al. Detection of fungal organisms in eosinophilic mucin using a fluorescein-labeled chitin-specific binding protein. Otolaryngol Head Neck Surg 2002; 127:377.
  66. Bush RK. Is topical antifungal therapy effective in the treatment of chronic rhinosinusitis? J Allergy Clin Immunol 2005; 115:123.
  67. Inoue Y, Matsuwaki Y, Shin SH, et al. Nonpathogenic, environmental fungi induce activation and degranulation of human eosinophils. J Immunol 2005; 175:5439.
  68. Kheradmand F, Kiss A, Xu J, et al. A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease. J Immunol 2002; 169:5904.
  69. Kuhn DM, Ghannoum MA. Indoor mold, toxigenic fungi, and Stachybotrys chartarum: infectious disease perspective. Clin Microbiol Rev 2003; 16:144.
  70. Hodgson MJ, Morey P, Leung WY, et al. Building-associated pulmonary disease from exposure to Stachybotrys chartarum and Aspergillus versicolor. J Occup Environ Med 1998; 40:241.
  71. Johanning E, Biagini R, Hull D, et al. Health and immunology study following exposure to toxigenic fungi (Stachybotrys chartarum) in a water-damaged office environment. Int Arch Occup Environ Health 1996; 68:207.
  72. Al-Ahmad M, Manno M, Ng V, et al. Symptoms after mould exposure including Stachybotrys chartarum, and comparison with darkroom disease. Allergy 2010; 65:245.
  73. McGinnis MR. Pathogenesis of indoor fungal diseases. Med Mycol 2004; 42:107.
  74. Weichel M, Schmid-Grendelmeier P, Rhyner C, et al. Immunoglobulin E-binding and skin test reactivity to hydrophobin HCh-1 from Cladosporium herbarum, the first allergenic cell wall component of fungi. Clin Exp Allergy 2003; 33:72.
  75. Hudnell HK, Otto DA, House DE, Mølhave L. Exposure of humans to a volatile organic mixture. II. Sensory. Arch Environ Health 1992; 47:31.
  76. Korpi A, Järnberg J, Pasanen AL. Microbial volatile organic compounds. Crit Rev Toxicol 2009; 39:139.
  77. Kaminski E, Stawicki S, Wasowicz E. Volatile Flavor Compounds Produced by Molds of Aspergillus, Penicillium, and Fungi imperfecti. Appl Microbiol 1974; 27:1001.
  78. Larenas-Linnemann D, Baxi S, Phipatanakul W, et al. Clinical Evaluation and Management of Patients with Suspected Fungus Sensitivity. J Allergy Clin Immunol Pract 2016; 4:405.
  79. Kespohl S, Maryska S, Bünger J, et al. How to diagnose mould allergy? Comparison of skin prick tests with specific IgE results. Clin Exp Allergy 2016; 46:981.
  80. O'Driscoll BR, Powell G, Chew F, et al. Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma. Clin Exp Allergy 2009; 39:1677.
  81. Crameri R, Zeller S, Glaser AG, et al. Cross-reactivity among fungal allergens: a clinically relevant phenomenon? Mycoses 2009; 52:99.
  82. Morbidity Mortality Weekly Reports "Case Definitions for Chemical Poisonings." http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5401a1.htm (Accessed on February 07, 2011).
  83. Chew GL, Horner WE, Kennedy K, et al. Procedures to Assist Health Care Providers to Determine When Home Assessments for Potential Mold Exposure Are Warranted. J Allergy Clin Immunol Pract 2016; 4:417.
  84. Barnes CS, Horner WE, Kennedy K, et al. Home Assessment and Remediation. J Allergy Clin Immunol Pract 2016; 4:423.
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