Aspergillus fumigatus Sensitization Is Associated With High-Risk Bronchiectasis
Pei Yee Tiew1, Jayanth Kumar Narayana2, Tavleen Kaur Jaggi2
1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore.
Background:
Fungal sensitization is an increasingly recognized endophenotype in chronic respiratory disease; however, its role in bronchiectasis remains poorly defined. This study aimed to provide the most comprehensive evaluation to date of fungal sensitization and its clinical relevance in bronchiectasis using an expanded panel of crude and recombinant fungal allergens.
Research Question:
What are the prevalence and clinical implications of fungal sensitization in bronchiectasis?
Study Design And Methods:
An international, multicenter evaluation of fungal sensitization was conducted across 6 tertiary centers in 4 countries (Singapore, Malaysia, the United Kingdom, and Italy), prospectively recruiting 277 individuals with bronchiectasis. Using a comprehensive, expanded allergen panel including 11 crude and 24 recombinant fungal allergens (total of 35 allergens and 9,695 individual assays), sensitization responses were assessed in relation to clinical characteristics, exacerbation frequency, and geographic origin. Low baseline exacerbations were defined as < 3 and high baseline exacerbations as ≥ 3 in the preceding 12 months of study recruitment.
Results:
Our results showed that sensitization to recombinant Aspergillus fumigatus (rAsp f) was linked to bronchiectasis severity. Measurable responses to rAsp f allergens 12, 15, and 17 were associated with severe (hospitalized) exacerbations, particularly in those with low baseline exacerbations (low risk). "Sensitized" low-risk individuals exhibited significantly greater disease severity and higher occurrence of bronchiectasis-COPD overlap compared with nonsensitized, low-risk individuals, a relationship absent in those with high baseline exacerbations. Polysensitization to the same allergens conferred further additional risks of severe (hospitalized) exacerbations. Notably, Asian patients sensitized to rAsp f allergens 12, 15, and 17 exhibited the poorest clinical outcomes with increased symptoms, poorer lung function, and severe disease.
Interpretation:
This study shows that A fumigatus sensitization, particularly to rAsp f allergens 12, 15, and 17, is a clinically significant and potentially treatable trait in bronchiectasis. This finding is of highest relevance in individuals with lower baseline exacerbation frequency and of Asian descent.
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