Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively

Welsh, Kathryn G; Holden, Karl A; Wardlaw, Andrew J.; Satchwell, Jack; Monteiro, William; Pashley, Catherine H.; Gaillard, Erol

doi:10.1111/cea.13799

Cited by 26 publications

(41 citation statements)

References 50 publications

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“…Children with fungal sensitisation had evidence of more severe disease including worse lung function, demonstrating that the close link between fungal allergy and severe asthma seen in adults also holds true in children. 134…”

Section: Afad In Childrenmentioning

confidence: 99%

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Wardlaw¹,

Rick²,

Özyiğit³

et al. 2021

JAA

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Allergy to airway-colonising, thermotolerant, filamentous fungi represents a distinct eosinophilic endotype of often severe lung disease. This endotype, which particularly affects adult asthma, but also complicates other airway diseases and sometimes occurs de novo, has a heterogeneous presentation ranging from severe eosinophilic asthma to lobar collapse. Its hallmark is lung damage, characterised by fixed airflow obstruction (FAO), bronchiectasis and lung fibrosis. It has a number of monikers including severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis/mycosis (ABPA/ M), but these exclusive terms constitute only sub-sets of the condition. In order to capture the full extent of the syndrome we prefer the inclusive term allergic fungal airway disease (AFAD), the criteria for which are IgE sensitisation to relevant fungi in association with airway disease. The primary fungus involved is Aspergillus fumigatus, but a number of other thermotolerant species from several genera have been implicated. The unifying mechanism involves germination of inhaled fungal spores in the lung in the context of IgE sensitisation, leading to a persistent and vigorous eosinophilic inflammatory response in association with release of fungal proteases. Most allergenic fungi, including Alternaria and Cladosporium species, are not thermotolerant and cannot germinate in the airways so only act as aeroallergens and do not cause AFAD. Studies of the airway mycobiome have shown that A. fumigatus colonises the normal as much as the asthmatic airway, suggesting it is the tendency to become IgE-sensitised that is the critical triggering factor for AFAD rather than colonisation per se. Treatment is aimed at preventing exacerbations with glucocorticoids and increasingly by the use of anti-T2 biological therapies. Anti-fungal therapy has a limited place in management, but is an effective treatment for fungal bronchitis which complicates AFAD in about 10% of cases.

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Section: Afad In Childrenmentioning

confidence: 99%

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Wardlaw¹,

Rick²,

Özyiğit³

et al. 2021

JAA

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“…These children often become controlled when these factors are addressed. Modifiable factors include poor medication adherence, 22 exposure to environmental factors such as pet allergens 23 and other indoor allergens such as fungi, 13 exposure to tobacco smoke, 24 air pollution, 25 and psychosocial factors. 26…”

Section: Difficult-to-treat Asthmamentioning

confidence: 99%

“…12 Preschool disease markers predicting the development of severe asthma in older children are lacking; however, a recent study suggests that early sensitisation to thermotolerant fungi is associated with worse lung function in children with asthma. 13 Asthma severity is a spectrum but most children with asthma are controlled with regular use of low-to-medium doses of inhaled corticosteroids (ICS) with or without additional controller drugs. Severe asthma constitutes the extreme end of the asthma spectrum.…”

Section: Introductionmentioning

confidence: 99%

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction

Ramphul¹,

Lo²,

Gaillard³

2021

JAA

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Asthma is a heterogeneous disease, characterised by different phenotypes and endotypes. Precision medicine in asthma refers to the implementation of a targeted therapy for each individual child, based on the identification of treatable traits, including environmental, immunological and genetic factors. Severe asthma in children is associated with increased hospitalisation rates, a lower quality of life, increased healthcare costs and an increased mortality. In the era of new molecular biologics treatments, it is essential to improve deep phenotyping of children with severe asthma in order to deliver the most effective treatment to each individual child. In this review, we discuss the personalised approach to the assessment and management of severe asthma. We explore the indications and use of the currently licensed biologics, as well as the potential of other emerging treatments.

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“…These studies include cohorts from Europe, the USA and Asia, and test for sensitisation using between 3 and 7 fungal extracts from 12 genera, with Alternaria and Aspergillus being the two common to all 13 studies. In the paediatric studies dominated by children with mild to moderate asthma, Alternaria is the most common fungi causing sensitisation [ 49 , 50 ]. As disease severity increases, Aspergillus becomes the dominant allergen [ 51 ].…”

Section: Prevalence Of Afadmentioning

confidence: 99%

“…As such, there is likely to be a high level of cross-reactivity between the allergens and testing only with Alternaria from that group should be sufficient. Similarly, although as a research group we do currently include Aspergillus and Penicillium [ 29 , 49 , 64 , 65 ]; these represent two very closely related genera from the family Aspergillaceae. In our experience, sensitisation to the two fungi often co-occurs, with mono-sensitised individuals more frequently sensitised to A. fumigatus, suggesting P. chrysogenum could be excluded if resources are limited.…”

Section: Diagnosing Fungal Allergymentioning

confidence: 99%

Allergic fungal airways disease (AFAD): an under-recognised asthma endotype

Pashley

Wardlaw

2021

Mycopathologia

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The term allergic fungal airways disease has a liberal definition based on IgE sensitisation to thermotolerant fungi and evidence of fungal-related lung damage. It arose from a body of work looking into the role of fungi in asthma. Historically fungi were considered a rare complication of asthma, exemplified by allergic bronchopulmonary aspergillosis; however, there is a significant proportion of individuals with Aspergillus fumigatus sensitisation who do not meet these criteria, who are at high risk for the development of lung damage. The fungi that play a role in asthma can be divided into two groups; those that can grow at body temperature referred to as thermotolerant, which are capable of both infection and allergy, and those that cannot but can still act as allergens in IgE sensitised individuals. Sensitisation to thermotolerant filamentous fungi (Aspergillus and Penicillium), and not non-thermotolerant fungi (Alternaria and Cladosporium) is associated with lower lung function and radiological abnormalities (bronchiectasis, tree-in-bud, fleeting shadows, collapse/consolidation and fibrosis). For antifungals to play a role in treatment, the focus should be on fungi capable of growing in the airways thereby causing a persistent chronic allergenic stimulus and releasing tissue damaging proteases and other enzymes which may disrupt the airway epithelial barrier and cause mucosal damage and airway remodelling. All patients with IgE sensitisation to thermotolerant fungi in the context of asthma and other airway disease are at risk of progressive lung damage, and as such should be monitored closely.

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Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively

Cited by 26 publications

References 50 publications

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction

Allergic fungal airways disease (AFAD): an under-recognised asthma endotype

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