Fungus-associated asthma: overcoming challenges in diagnosis and treatment

Abstract

With regard to fungal colonization and fungal sensitization, the goals of fungus-associated asthma management are as follows: 1) to survey fungi colonizing the airways of patients repeatedly; 2) to evaluate the tendency of the colonizing fungi to sensitize patients and the influence on clinical manifestations of asthma; 3) to follow disease development to allergic bronchopulmonary mycosis or sinobronchial allergic mycosis; and 4) to determine whether fungal eradication from the airway of patients is beneficial from the viewpoints of future risk factors. Recent developments in molecular biological analyses have facilitated the identification of basidiomycetous fungi that were not previously thought to be of concern in fungal allergy. The total control of fungus-associated asthma will be accomplished by environmental management established from the viewpoint of both the ecology and life cycle of the responsible fungi.

Keywords::

• allergic bronchopulmonary mycosis
• antifungal drugs
• basidiomycetous fungi
• Bjerkandera adusta
• environmental control
• fungus-associated asthma
• fungus-colonized asthma
• fungus-sensitized asthma
• sinobronchial allergic mycosis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Fungi and molds are considered to be indoor or outdoor allergens, and fungal exposure is known to be associated with exacerbation of asthma.

• Fungal colonization due to continuous exposure to fungal allergens is considered to play a role in sensitizing asthmatic patients to the fungi or in enhancing clinical difficulty of treating asthma symptoms.

• When the responsible allergen is found to be environmental fungi, the treatment strategy is recommended to take into consideration the characteristics of the microbe, such as colonization or germination in the respiratory tract.

• Evaluating the results of skin tests and/or specific IgE antibodies would be significant for estimating the allergological background of asthma patients.

• As lung function declines calculated based on changes in forced expiratory volume in 1 s (FEV1) at only two different points are easily influenced by the daily condition of asthma, for closer estimation, the annual decline in postbronchodilator FEV1 (δ FEV1 ml/year) should be calculated by single regression analysis using data from at least five evaluations over more than 5 years.

• Stratified analysis according to the presence of the respective fungus should be performed when planning clinical studies against fungal sensitization asthma.

• Patients with both positive culture and positive sensitization to some fungi may demonstrate particular clinical manifestations as a new phenotype of asthma under conditions of chronic exposure to such fungi.

• The fact that same species of fungi are repeatedly cultured from the same patients is one of the key points to decide to commence investigation of the correlation between asthma and the fungi.

• Recent developments in molecular biological analyses have facilitated the identification of non-sporulating molds, and have increased the list of environmental fungi that were not previously thought to be of concern as pathogenic agents.

• It is becoming increasingly important to pay attention to basidiomycetous fungi in addition to classical environmental fungi in fungus-associated asthma. The influence of these fungi on the clinical manifestations of asthma should be elucidated in the near future.

• The predominance of Bjerkandera adusta rather than of Schizophyllum commune in asthma patients is noteworthy. Thus, among the approximately 31,000 species in the basidiomycetous phylum, these additional two fungi should be taken into consideration when managing fungus-associated asthma.

• Considering both the high prevalence of this fungus in allergic bronchopulmonary mycosis and the fundamental similarity in therapy for both disorders occurring in the same individual, it will be helpful to develop simplified guidance for S. commune-associated sinobronchial allergic mycosis from the viewpoint of Schizophyllum allergy.

• Although there may be room to reconsider the appropriate dose and duration of antifungal drug administration in such studies, other effects such as decreasing the frequency of exacerbation of asthma or improvement of laryngeal sensations should be estimated appropriately.

• Without considering the role of fungal colonization for sensitization in patients with fungus-associated asthma, it would not be possible to achieve successful treatment with antifungal drugs.

• The control of the recurrence of fungus-associated asthma, which seemed to be influenced by the presence of the respective fungi in the environment, will be accomplished by environmental management.