Fungi in Asthma: From Epidemiology and Airway Mycobiome to Molecular Mechanisms and Novel Allergenic Phytopathogens

Fungal exposure and sensitization are linked to asthma severity, but their clinical significance varies by host, exposure context, and disease phenotype. This review integrates epidemiological, immunological, and clinical evidence on fungal-associated asthma, distinguishing environmental exposure, allergic sensitization, and persistent airway colonization. We examine how fungal allergens, proteases, and cell-wall components engage pattern-recognition receptors, disrupt epithelial barriers, and activate overlapping type 2 and type 17 inflammatory pathways. Studies of the airway and intestinal mycobiome offer additional perspectives on host–fungal interactions, although most human findings remain associative and do not establish causality or clinical utility. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are distinct clinical contexts that require different diagnostic and therapeutic approaches. Antifungal treatment has an established role in ABPA, whereas evidence in SAFS is inconsistent; biologic selection should be guided by clinical phenotype and established eligibility criteria rather than fungal sensitization alone. We also synthesize our published biochemical, epithelial-cell, and murine studies of seven plant-associated fungal and oomycete taxa from eastern Poland. These findings support further investigation of their allergenic and pro-inflammatory potential but do not establish clinical allergenicity or predict treatment response in humans. Priorities include standardized exposure assessment, validated diagnostic reagents, and longitudinal studies linking fungal measurements to clinical outcomes. Expanded allergen panels and mycobiome-based approaches require prospective validation before routine clinical implementation.