Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Bronchiectasis exhibit a broad range of clinical presentation including overlap. Such disease heterogeneity between patients highlights the need for increased personalisation including endo-phenotyping efforts to improve our understanding of disease pathogenesis and progression. Fungal moulds are ubiquitous, and their spores inhaled daily in large numbers into the airway. Removed by intact anatomical barriers and an effective immune response, disease occurrence in chronic respiratory disease states is dictated by the host immune system and virulence of the infecting fungal strain. Patients with chronic respiratory diseases including asthma, COPD and bronchiectasis are at significant risks of acquisition, colonization, infection, and allergic responses to various fungi including Aspergillus. Use of next generation sequencing has revolutionised our detection and understanding of the airway microbiome in these settings including its functionality. How best to apply this information into patient care, monitoring and treatment based on fungal airway signatures however remains challenging. Using asthma, COPD, and bronchiectasis as models of respiratory disease, this talk will summarize work performed by our group illustrating the importance of the sensitization, allergy and mycobiome analysis in asthma, COPD and bronchiectasis, which reveal important and clinically relevant microbial signatures based on Aspergillus and discuss how environmental microbiomes can be leveraged for clinical application in the era of next generation sequencing and precision medicine.