The clinical differences of asthma in patients with molds allergy

Krzysztof Kołodziejczyk1, Andrzej Bożek2, Jerzy Jarząb2, Radosław Gawlik3

1Allergy Outpatient Clinic, Katowice, Poland

2Clinical Department of Internal Medicine, Dermatology and Allergology, Medical University of Silesia, Katowice, Poland

3Clinical Department of Internal Disease, Allergology and Immunology, Medical University of Silesia, Katowice, Poland



The clinical differences of asthma in patients with molds allergy

The authors declare no financial disclosure




Introduction: Bronchial asthma is an increasing problem worldwide. The course of bronchial asthma is dependent on the type of inducing allergens. The differences between the clinical features of asthma in patients with monovalent allergies to molds and with other allergies were explored.

Material and methods: Randomly selected 1910 patients (924 women and 986 men) between 18−86 years in age were analyzed according to type of allergy and asthma. The diagnosis of asthma was confirmed on the basis of GINA criteria, physical examination and spirometry. Allergy diagnosis was confirmed on the basis of medical history, a positive skin prick test and the measurement of serum-specific IgE to inhalant allergens, using an extended profile of mold allergens.

Results: Patients with monovalent allergies to molds (4% of analyzed group) had significantly more frequent diagnoses of asthma than patients in the other group (53% vs. 27.1−32.4%, p < 0.05). Patients with allergies to Alternaria alternata had an odds ratio of 2.11 (95%CI: 1.86−2.32) for receiving a diagnosis of bronchial asthma. They had less control over their asthma, which was more severe compared to patients with other allergies. Patients with asthma and allergies to mold had significantly more frequent exacerbation of asthma requiring systemic corticosteroids and/or hospitalization. They used a significantly greater mean daily dose of inhaled steroids compared to other patients.

Conclusion: Patients with monovalent IgE allergies to molds are at a higher risk for asthma than patients with other allergies. Their asthma is often more intense and less controlled compared to that of patients with other types of allergies.


Key words: asthma, molds, allergy

Pneumonol Alergol Pol 2016; 84: 81–86



Bronchial asthma is an increasing problem in all age groups. According to the WHO, between 100 and 150 million people around the world suffer from asthma, and this number is rising. Worldwide, deaths from this condition have reached over 180,000 annually [1]. There are a number of documents relating to the diagnosis and treatment of bronchial asthma, but our knowledge is incomplete in some fields [2−4]. The natural course of asthma is dependent on many factors, such as the type of inducing allergens. The majority of the available literature is devoted to mites, pollen and professional allergens, while less attention has been paid to animal (except cats) or mold allergens. Molds are extensive source of allergens. Exposure and sensitization to fungal allergens can promote the development and worsening of allergic diseases. Although numerous species of fungi have been associated with allergic diseases in the literature, the significance of fungi from the genera Alternaria, Cladosporium, Penicillium, and Aspergillus has been well documented [5].

The clinical spectrum of hypersensitivity reactions elicited by molds is very broad; in addition to IgE-mediated type I allergies, it includes type II, III and IV reactions, which are defined according to the criteria proposed by Coombs and Gell [6]. Clinically, IgE-mediated sensitization to mold allergens can manifest as allergic rhinitis and rhinosinusitis, atopic dermatitis and allergic asthma [6].

Some information has been published regarding the differences in the nature of asthma in patients with allergies to molds [6, 7]. However, we still lack detailed information on this issue. Additionally, the precise prevalence of fungal sensitivities remains unclear.

The aim of this study was to attempt to assess the differences between the clinical features of asthma in patients with monovalent allergies to molds and those with other allergies. This could be the starting point to draw attention to the special needs of these patients.


Material and methods


32 654 patients from Outpatient Allergological Clinics were prescreened in data bases. 1910 subjects: 924 women and 986 men between 18−86 years were randomly selected. They were analyzed according to their types of allergy and asthma.

The diagnosis of asthma was based on GINA criteria [2], physical examination and spirometry with a positive result on the reversibility test (Lung test 1000). A positive test result was defined in accordance with the criteria of the ATS-ERS [8, 9]. Before testing, the patients did not use short-acting beta2 agonists for 8 hours, ipratropium derivatives or theophylline derivatives for 24 hours, long-acting beta2 agonists for 48 hours, and tiotropium derivatives for 72 hours. Smokers were asked to abstain from smoking for 1 hour before testing. The test was deferred for 4 weeks in cases of respiratory tract infections.

The allergy diagnosis was confirmed on the basis of history, positive skin prick tests (SPT) and measurements of concentrations of serum-specific IgE (sIgE) in response to inhalant allergens.

SPT (Allergopharma, Germany) was performed using the following allergens: D. pteronyssinus, D. farinae, mixed grass, mixed tree, birch, alder, hazel, mugwort, and the molds Aspergillus fumigatus, Cladosporium herbarum, Botrytis cinerea, Alternaria alternata, Curvularia lunata, Penicillium notatum, Fusarium moniliforme, Helminthosporium solani, Mucor mucedo, Trichophyton mentagrophytes, Rhizopus nigricans, Pullularia pullulans, Neurospora sitophila, Candida albicans, and Serpula lacrymans. Positive (histamine 10 mg/ml) and negative (a saline control) tests were included. Allergy was defined as having a positive skin test result for at least one allergen with a wheal max. diameter of at least 3 mm greater than that of the negative control. Patients with negative tests for histamine were excluded from further analyses.

The response of serum immunoglobulin levels (serum sIgE) to all mentioned allergens were measured using the Phadia Laboratory System (Phadia AB, Uppsala, Sweden), an immunoenzymatic test. The results were assessed as positive when the serum sIgE concentration was > 0.75 IU/ml (class II according to the manufacturer’s brochure) [10]. After the initial analysis, 1475 patients with allergies and/or asthma were classified into four groups:

— Patients with monovalent allergies to molds, group M.

— Patients with monovalent allergies to house dust mites, group D.

— Patients with monovalent allergies to pollens (grass and/or trees and/or mugwort), group P.

— Patients with multivalent allergies (allergies to at least two groups of allergies, including house dust mites, molds, and pollens), group V.

The monovalent allergy was confirmed as followed: typical clinical symptoms (positive result of original questionnaire), positive skin prick test and/or allergen specific IgE to any allergen mold and negative results to other analyzed, inhalant allergens. Other monovalent allergies were diagnosed in a similar way.

The characteristics of the groups are shown in Table 1.


Table 1. Characteristics of the study groups

Patients included in the analysis, n = 1475


group M

n = 64

group D

n = 383

group P

n = 388

group V

n = 415

Mean age

38.1 ± 19.1

43.2 ± 10.5

36.7 ± 11.9

34.8 ± 10.3

Female (%)





Duration of allergy in years (± SD)

8.2 ± 3.7

6.9 ± 1.4

6.8 ± 6.2

6.2 ± 4.9

Residence: village





Smoking (current or former)





Higher education





Allergy in the family





Allergy in childhood





SD — standard deviation; group M — monovalent allergy to molds; group D — monovalent allergy to house dust mites; group P — monovalent allergy to pollens; group V — multivalent allergy; *significant differences for p < 0.05


Study protocol

Each subject completed the Asthma Control Test (ATC) [11] and an original questionnaire about mold allergies (Table 2).


Table 2. Original questionnaire about allergies to fungi

Do your disease symptoms, such as runny nose, cough, shortness of breath, and watery or itchy eyes, occur in the period from June to August and/or in the autumn and winter months?


Are your symptoms associated with being in humid areas, such as basements, old houses and other premises, where mold is visible on the wall?


Do similar symptoms as listed in paragraph 1 arise when you stay in a steamy bathroom?


Do similar symptoms occur during sleep in your bed?


Do you live in a home where there is visible mold on the walls?


Do you have allergic symptoms (at least one of the following symptoms: rash, cough, shortness of breath, runny nose, abdominal pain, or diarrhea) after eating any of these foods: yeast dough, moldy cheeses, red wine, or pickled preserves?


Have you ever had a confirmed allergic skin test or blood test IgE sensitization to mold fungi?


Do you have asthma-like symptoms (coughing or difficulty in breathing) that require treatment in the summer?


Do you suffer from bronchial asthma and are using drugs?


Does anyone in your family have a known allergy to molds?


Does the presence of a large number of potted plants have an effect on your disease symptoms?


Do you badly tolerate staying in air-conditioned rooms or in the car with the air conditioner?



The study was approved by the local ethics committee (Medical University of Silesia, Katowice, Poland). All patients signed an informed consent form.


Statistical analysis

Data with a normal distribution, such as participant age, disease duration and spirometric test results were compared using Student’s t-test for independent samples. Odds ratios were calculated to assess the likelihood of asthma in the presence of a particular trait in the subjects. Kruskal-Wallis test was used to compare non-parametric variables between the groups. P < 0.05 was considered statistically significant.



Patients with monovalent allergy to molds represented 4.3% of all respondents with inhalant allergy. The original questionnaire about mold allergies indicated the special importance of patient exposure to damp basements (89% of the patients with allergies to mold answered YES to the second question and the questions about steamy bathrooms; 86% of respondents answered YES to the third question) in describing the symptoms of allergies to mold fungi. The questionnaire results from the control groups without allergies to molds were significantly negative in relation to the study group for all of the targeted questions.

Patients with monovalent allergies to mold had significantly more diagnoses of asthma than the patients in the other analyzed groups: 53% (34 subjects) vs. 32.4% (124) in group D vs. 27.1% (105) in group P and vs. 29.2% (121) in group V (p < 0.05). There were no correlation between diagnosis of asthma and age or sex in all analyzed groups.


IgE-specific skin prick tests

In the group of patients monosensitized to molds, allergies to the following species dominated: Alternaria alternata in 57.2% of patients (based on a positive SPT and/or sIgE), Cladosporium herbarum in 40.9% of patients, Aspergillus fumigatus in 34.7% of patients, Mucor mucedo in 30.1% of patients, Trichophyton mentagrophytes in 21.2% of patients and Fusarium moniliforme in 19.1% of patients. Other allergens occurred in less than 20% of the patients.

In group M, patients with diagnoses of varying degrees of bronchial asthma had similar profiles to those with mold allergies. However, patients with allergies to Aspergillus fumigatus and Trichophyton mentagrophytes were significantly more likely to suffer from severe asthma. The detailed results are shown in Table 3.


Table 3. Profile of mold allergies in group M (% of patients) according to asthma severity

Allergy to mold species

Episodic asthma

Mild or moderate


Severe asthma


Alternaria alternata





Cladosporium herbarum





Aspergillus fumigatus




> 0.05

Mucor mucedo





Trichophyton mentagrophytes




> 0.05

Fusarium moniliforme





Other species





NS — no significant differences


Additionally, patients with an allergy to Alternaria alternata had an odds ratio of 2.11 (95%CI: 1.86−2.32) of receiving a diagnosis of bronchial asthma.

Furthermore, they had less control over their asthma, which was more severe compared to that of patients with other allergies (Table 4). Patients with both asthma and allergies to mold had significantly more exacerbated asthma requiring systemic corticosteroids and/or hospitalization. The results are shown in Figure 1.


Table 4. Characteristics of bronchial asthma in patients with different types of allergies


Patients with asthma diagnoses


group M

n = 32 (%)

group D

n = 124 (%)

group P

n = 105 (%)

group V

n = 121 (%)

Mean age

42.9 ± 10.4

44.1 ± 13.9

42.1 ± 10.2

39.5 ± 8.9


Female (%)

16 (47.1)

60 (48.4)

45 (42.9)

53 (43.8)


Duration of asthma

10.4 ± 5.2

9.2 ± 5.1

9.7 ± 3.6

9.3 ± 6.3


Mean result of ACT

11.9 ± 3.1*

15.9 ± 4.8

19.7 ± 3.7

18.5 ± 7.4

< 0.05

Severe asthma (%)

8 (26.5)*

18 (14.5)

11 (10.5)

15 (12.4)

< 0.05

Moderate asthma (%)

9 (26.8)

35 (28.2)

30 (24.2)

32 (26.4)


Mild asthma (%)

12 (35.3)

43 (34.7)

39 (37.2)

47 (38.8)


Episodic asthma (%)

5 (14.7)*

28 (22.5)

25 (23.8)

27 (22.3)

< 0.05

Fully control asthma

11 (32.4)*

58 (46.8)

49 (46.7)

54 (44.6)

< 0.01

Partially controlled asthma

10 (29.4)

32 (25.8)

35 (33.3)

36 (29.8)


Uncontrolled asthma

13 (29.4)*

34 (27.4)

21 (20)

31 (25.6)

< 0.01

Allergic rhinitis

30 (88.2)

108 (87.1)

97 (92.4)

107 (88.4)


Degree of asthma control according to the GINA; ACT — asthma control test; *Significant difference for p < 0.05


group M — monovalent allergy to molds; group D — monovalent allergy to house dust mites; group P — monovalent allergy to pollens; group V — multivalent allergy; *significant differences for p < 0.05

Figure 1. The number of asthma exacerbations per year and hospitalizations caused by asthma in the study groups


Patients with both asthma and allergies to mold used a significantly greater mean daily dose of inhaled steroids compared to patients with other types of allergies and asthma; the use of fluticasone propionate in the groups was 730 ± 425* mcg vs. 430 ± 225 mcg vs. 470 ± 165 mcg vs. 340 ± 140 mcg (p < 0.05).



The obtained results indicate the important problem of bronchial asthma in patients with allergies to mold. Of the analyzed allergic patients, those with monovalent allergies to mold had significantly more frequent diagnoses of asthma. In this group, patients with allergies to Alternaria were predominant. This finding is consistent with previous observations. Alternaria is a major environmental allergen associated with asthma and allergic rhinitis [12, 13]. Alternaria spp. are generally considered to be outdoor fungi, although they also exist in indoor environments [5, 14]. Airborne outdoor Alternaria spores are detectable from May to November, with the highest levels occurring in cultivated areas containing grasslands and grain [14]. The clinical significance of A. alternata as a respiratory allergen has been well documented. Studies have revealed a strong association between sensitization to Alternaria spp. and the presence of asthma or allergic rhinitis, as well as the severity of asthma [5, 15, 16]. In addition, sensitization and exposure to Alternaria has been associated with epidemics of severe asthma exacerbation, including respiratory arrest [17]. Thunderstorms appear to be a contributing factor to high levels of fungal spores and epidemics of asthma exacerbation [5].

We found that sensitivities to two molds, Aspergillus fumigatus and Trichophyton mentagrophytes, were more common in patients with severe asthma than in others. Aspergillus, Penicillium, Alternaria and Cladosporium, play important roles in the induction of asthma as well as in its intensity patterns [6, 7]. Aspergillus fumigatus can cause allergic bronchopulmonary aspergillosis, which is characterized by its exacerbation of asthma, recurrent transient infiltrates on radiographic images, coughing up of thick mucus plugs, peripheral and pulmonary eosinophilia, and increased total serum IgE and specific IgE levels, especially during exacerbation [18]. In this study, five patients with bronchial asthma, allergy to molds and episode of bronchopulmonary aspergillosis were observed. The importance of Trichophyton mentagrophytes had not been previously confirmed. Fungi in the genus Trichophyton are known to be the causal pathogens of dermatophytosis, a fungal infection of the skin, hair and nails. Trichophyton rubrum and Trichophyton mentagrophytes are the most common pathogens in the genus [5]. However, the route of exposure to Trichophyton allergens in such Trichophyton-infected patients has not been identified. A few reports have suggested the possible role of inhaled Trichophyton in the pathogenesis of asthma or rhinoconjunctivitis among subjects without Trichophyton infections [19, 20]. Occupational exposure to airborne Trichophyton in nail dust has been shown to induce nasal and eye symptoms in chiropodists [21]. There was no such data in our study. Sensitization to Trichophyton is also reported to be a risk factor for more severe disease among the general asthmatic population [22, 23]. However, there is no published information regarding whether a potential correlation exists between Trichophyton and asthma severity.

An important limitation of this study is our testing of IgE-dependent responses only. There is evidence that these species of molds also induce type II, III and IV reactions [6]. Thus, the obtained results about the roles of different types of molds on asthma are not final.

Worse asthma control, a greater number of exacerbations and the need for larger doses of inhaled steroids are the results of the higher prevalence of severe asthma that was observed in this study. The important role of fungi in the exacerbation of asthma has been confirmed in previous literature. TNF-alpha as well as IFN-alpha are secreted by fungi-prestimulated leukocytes from the lower respiratory tract and may be involved in the processes of exacerbation of asthma complicated by fungal infections [24]. However, further details on this role have not been provided [2, 6, 12, 16].



The obtained data suggest that patients with monovalent IgE allergies to mold are more at risk for asthma than patients with other allergies. These patients require more attention because their asthma is often more severe and less controlled than that of patients with other types of allergies.


Conflict of interest

The authors declare no conflict of interest.


Address for correspondence: Andrzej Bożek, Clinical Department of Internal Medicine, Dermatology and Allergology, Medical University of Silesia, Katowice, e-mail:


Received: 16.12.2015



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