Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study

Abstract

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.

Bronchiectasis and cough: An old relationship in need of renewed attention

“…The importance of microbes in bronchiectasis is further substantiated through culture-independent analysis of the lung microbiome illustrating the influence of macrolide therapy on microbiome composition and the association of microbial consortia with important clinical outcomes including exacerbation [33,34]. Work from our group and others has extensively characterised the fungal component of the bronchiectasis microbiome (the Mycobiome) and highlights a high frequency of fungal sensitisation associated with worsening disease severity, lung function and exacerbations [35]. In chronic cough, microbiome analysis has been applied to paediatric patients which has illustrated an increased abundance of commensal taxa in the lower airway and the potential association of specific microbiome signatures with particular patients including asthma, bacterial bronchitis or neurologically impaired orally fed subjects [36].…”

“…Therapies such as use of antitussives, inhaled corticosteroids (ICS) or chest physiotherapy may therefore alleviate symptoms in individuals with problematic cough if appropriately targeted [10,22]. While bronchiectasis mandates multifaceted management with consideration of heterogeneous clinical features, co-morbidities, microbiology, inflammation and therapeutic responses, cough remains an important common phenotypic trait but also a key symptom in the definition of a bronchiectasis exacerbationa major endpoint applied in almost all clinical trials and an important prognostic indicator of disease progression [23,24].…”

“…Effects were most pronounced in specific patient subgroupssuch as those colonised by basidiomycetous fungireinforcing the importance of microbiology and the targeted, personalised approach likely required. The potential application of antifungal therapeutics in bronchiectasis should however be targeted to specific disease subtypes, such as those driven by fungal allergy and, here, the identity of the inciting fungal species may be critically important [4,5,10,35,56].…”

“…This provides a plausible framework for the emergence of specific microbe-driven cough phenotypes in bronchiectasis. The role of fungi in bronchiectasis remains an active area of research by our group and others [35,[81][82][83]. The presence of fungi, in particular those of the genus Aspergillus, is of clear clinical significance in bronchiectasis and associated with a spectrum of disease phenotypes that range from chronic pulmonary aspergillosis (CPA), asymptomatic colonisation, fungal sensitisation and allergic bronchopulmonary aspergillosis (ABPA) [81,83].…”

The microbiome in bronchiectasis: Cutting a lung story short

“…Additional measures of severity including composite scales such as the bronchiectasis severity index and symptom questionnaires would be valuable for comprehensive disease evaluation . Ideally, future studies should evaluate the impact of antibiotic treatment as well as moving beyond the bacteriome to include fungi, viruses and mycobacteria …”