In the case of fungi, the origin can be either the URT (e.g., spp.) or the continuous inhalation of spores that are present in the environment (e.g., most filamentous fungi) [48,66,73,92]. by interacting with bacterial species and with the hosts physiology. In this article, we review the current knowledge on the role of fungi in chronic respiratory diseases, which was obtained by conventional culture and next-generation sequencing, highlighting the limitations of both techniques and exploring gamma-secretase modulator 2 future research areas. is recognised as the microorganism with the greatest impact on lung function; however, the role of fungi in CF lung disease has always been controversial [12,13]. The recent use of culture-independent microbiological techniques based on deep sequencing, also known as next-generation sequencing (NGS), has shown that the respiratory tract of healthy individuals is not sterile, as formerly thought, but composed of a complex microbial community, the microbiome. Most studies on this subject have focused on the bacterial component of this microbiome, whereas other organisms such as viruses (virome) and fungi (mycobiome) have been less-investigated. The term mycobiota refers to the fungal component of a given microbial community, whereas mycobiome refers to their corresponding genomes [14]. It has been shown that the microbial communities present in the lungs of patients with CRD significantly differ from those of healthy individuals due to the disruption of microbial homeostasis, which is referred to as dysbiosis. These changes include not only those related to the microbiome composition but also changes in total microbial content as well as their abundance [14]. There is growing evidence that the lung mycobiome has a significant impact on the clinical outcome of CRD. Thanks to culture-independent methods, especially NGS, several fungi that were gamma-secretase modulator 2 previously undetected by classical culture methods have been identified in human lungs. Molecular studies have shown that gamma-secretase modulator 2 the structure and diversity of the lung mycobiota vary between differing populations (healthy individuals and those with various diseases) and this variation could play a role in CRD. Moreover, the interaction between the mycobiome and bacteriome and/or virome appears to be a cofactor of inflammation and host immune response, thereby contributing to the decline in lung function and disease progression [15]. In this review, we will focus on the prevalence of fungal isolation and its clinical significance in CRD and summarise the conclusions drawn from the NGS study of the lung mycobiota. 2. Prevalence and Clinical Significance of Fungi in Chronic Respiratory Disease 2.1. Chronic Obstructive Pulmonary Disease The prevalence of fungal infection in COPD has not been as extensively studied as bacterial infection. This detection depends on whether acute or stable patients are evaluated and, above all, on the techniques used to recognise the fungi, which include fungal cultures, nucleic acid detection, sensitisation, and specific markers for specific fungal species, such as galactomannan antigen for [16,17]. The prevalence of chronic fungal infection MPH1 is, therefore, variable and seldom studied. Studies have placed the prevalence of fungal infection at varying rates that are close to 20% [16,17,18,19], which represents a substantial prevalence. However, Bafadhel et al. (2011) showed that approximately 50% of stable patients with COPD at baseline had culturable filamentous fungi, 75% of which were [20]. Of the hospitalised patients with COPD, 1.3C3.9% develop invasive aspergillosis, based on positive cultures of spp. and radiological findings [17]. Fungal sensitisation appears to play an important role in the clinical presentation and progression of COPD [21]. Again, the way in which fungal infection is studied should be considered when interpreting these results. Probably the most consistently described clinical effect is the relationship between fungal infection and the risk of exacerbations independent of COPD severity and stage [22]. A number of authors have suggested that the frequency of detection in patients with COPD might be associated with the early Global Initiative for Chronic Obstructive Lung Disease stages [16]; however, this finding requires further scrutiny. An interesting association between fungi and COPD relates to the use of inhaled corticosteroids. Various studies gamma-secretase modulator 2 have shown that corticosteroid therapy is associated with increased filamentous fungal burden in allergic fungal disease [20,23]. There is increasing.