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Tuesday, February 7, 2012

An overview of allergic lower respiratory illnesses associated with fungi

Allergy to molds is known to be correlated with the development and severity of asthma, with Aspergillus fumigatus, in particular, associated with persistent, severe asthma in adults. A. fumigatus is the cause of allergic bronchopulmonary aspergillosis (ABPA), an asthma co-morbidity that results in exacerbations, recurrent transient chest infiltrates, peripheral and pulmonary eosinophilia, thick mucus expectorates, elevated IgE, and persistent colonization of the lower lung.

Knutsen and colleagues from the AAAAI’s Fungi and Lower Respiratory Disease Task Force present a comprehensive discourse on fungi implicated in allergic lower lung diseases in this month’s issue (J Allergy Clin Immunol 2012;129:208-291). The authors begin briefly discussing mold sensitivity and asthma, prevalence of fungal sensitivity, and relative risk of fungal sensitization and negative respiratory outcomes. They discuss the environmental ecology and biology of airborne fungi, common indoor and outdoor fungi, and fungal allergens recognized in the most common pathogenic fungi, Aspergillus fumigatus, Penicillium spp., Alternaria alternata, and Cladosporium herbarum.

The authors point out the ABPA is the most common form of allergic bronchopulmonary mycosis (ABPM), though Candida and Penicillium are also causal fungi in ABPM. In the absence of ABPM, fungal colonization in severe asthma is common and occurs with and without sensitization. Knutsen et al. note that fungal sensitization is associated with adverse clinical presentations. Diagnostic work up of fungal sensitization in asthma includes skin prick testing and serum specific IgE and the authors discuss congruence between skin testing and specific IgE results.

Knutsen et al. extensively cover the pathophysiology of allergic fungal airway diseases, including the role of dectin receptors, proteases and protease-activated receptors, chitinases, and mycotoxins. Genetic polymorphisms identified in genes coding HLA class II, IL4 receptor, IL-13, and TLRs in patients with ABPA are briefly reviewed.

The authors conclude with a discussion of treatment approaches for ABPA and severe asthma with fungal sensitization (SAFS). Oral corticosteroids dosed for 3-6 weeks are indicated for ABPA exacerbations. Greater than half of ABPA patients respond to itraconazole therapy, for which a minimum of 6 months of therapy is recommended. Knutsen et al. note that itraconazole therapy can be extended safely for years in patients that tolerate it.

We asked Dr. Knutsen to tell us about research gaps identified by the committee. He sent us the following list of research questions that have been identified as requiring further discussion:

· Clarifying the contributions of environmental (in home, local) and microbial triggers on activity and severity of fungal asthma and allergic bronchopulmonary mycosis

· Determining the effects of climate change on disease severity and exacerbations of fungal asthma

· Improving the understanding the role of genetic, epigenetic and innate and adaptive immunity in protection from and susceptibility to Aspergilli in atopic patients, patients with fungal asthma and patients with allergic bronchopulmonary mycosis

· Learning the role of the microbiome and monitoring changes in association with treatment and exacerbations

· Determining the utility and validity of diagnostic tests for skin testing and in vitro detection of IgE antibodies

· Developing epidemiology, diagnosis and treatment consortia to create registries and respositories to reach agreement on uniform, essential criteria for diagnosis of allergic bronchopulmonary mycosis and severe asthma with fungal sensitization and its treatment

· Exploring the contributions of co-morbidities including chronic rhinosinusitis or allergic fungal rhinosinusitis in patients with fungal asthma, severe asthma with fungal sensitization and in allergic bronchopulmonary mycosis

· Identifying pharmacogenetic pathways and therapeutic heterogeneity in fungal diseases of the lower airways

· Exploring whether severe asthma with fungal sensitization meets criteria as an endotype of asthma with distinctive pathogenesis and response to treatment

· Discovering novel therapies and treatment regimens to prevent bronchiectasis in allergic bronchopulmonary mycosis

· Determining factors associated with remission of allergic bronchopulmonary mycosis and reduction in severity of fungal asthma

· Clarifying uses of bio markers and patterns of inflammation that identify stages of allergic bronchopulmonary mycosis or mild versus severe persistent asthma with fungal sensitization

· Demonstrating whether advanced recovery methodology for fungi in sputum is associated with disease activity and responses to treatment

· Elucidating the susceptibility of women to allergic bronchopulmonary mycosis and fungal asthma

· Utilizing improvements in radiologic scanning for early diagnosis and identification of exacerbations of allergic bronchopulmonary mycosis

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