Epithelial-to-mesenchymal transition (EMT) is a reversible process, in which epithelial cells lose their epithelial traits and acquire a mesenchymal phenotype. This transformation has been described in different lung diseases, such as lung cancer, interstitial lung diseases, asthma, chronic obstructive pulmonary disease and other muco-obstructive lung diseases, such as cystic fibrosis and non-cystic fibrosis bronchiectasis. The exaggerated chronic inflammation typical of these pulmonary diseases can induce molecular reprogramming with subsequent self-sustaining aberrant and excessive profibrotic tissue repair. Over time this process leads to structural changes with progressive organ dysfunction and lung function impairment. Although having common signalling pathways, specific triggers and regulation mechanisms might be present in each disease. This review aims to describe the various mechanisms associated with fibrotic changes and airway remodelling involved in chronic airway diseases. Having better knowledge of the mechanisms underlying the EMT process may help us to identify specific targets and thus lead to the development of novel therapeutic strategies to prevent or limit the onset of irreversible structural changes.

Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein, expressed on the apical surface of epithelial cells. CFTR absence/dysfunction results in ion imbalance and airway surface dehydration that severely compromise the CF airway microenvironment, increasing infection susceptibility. Recently, novel therapies aimed at correcting the basic CFTR defect have become available, leading to substantial clinical improvement of CF patients. The restoration or increase of CFTR function affects the airway microenvironment, improving local defence mechanisms. CFTR modulator drugs might therefore affect the development of chronic airway infections and/or improve the status of existing infections in CF. Thus far, however, the full extent of these effects of CFTR-modulators, especially in the long-term remains still unknown. This review aims to provide an overview of current evidence on the potential impact of CFTR modulators on airway infections in CF. Their role in affecting CF microbiology, the susceptibility to infections as well as the potential efficacy of their use in preventing/decreasing the development of chronic lung infections and the recurrent acute exacerbations in CF will be critically analysed.

Background: intravenous Fosfomycin (ivFO) is an antibiotic with a broad antimicrobial spectrum, covering both Gram- and Gram+ pathogens. Literature proves it to be a valid option in pulmonary exacerbations (PEx) in patients (pt) with Cystic Fibrosis (pwCF). Pt with bronchiectasis of other aetiology (pwNCFB) have not been previously studied. Aim: describe effectiveness and safety of ivFO for PEx in pwCF and pwNCFB. Methods: a retrospective analysis on pwCF and pwNCFB treated for PEx in hospital with ivFO in our adult CF Centre from 1.1.18 to 31.12.22 was performed. 49 pt were included (32 pwFC; mean age 42 ys (19-85), mean FEV1pp 50 (19-109), receiving a total of 107 courses (mean courses/pt 2.18 (1-11)). All had P. aeruginosa chronic infection and many had coinfections: S. aureus Methicillin-Sensitive (19) and Resistant (8), Achromobacter spp (8), E. coli (7), S. maltophilia (1), Acinetobacter spp (4), P. mirabilis (3). In all ivFO was associated with another antibiotic: Piperacillin/Tazobactam (35), Ceftazidime (21), Tobramycin (13), Meropenem (23), Imipenem/Cilastatin (8), Ceftazidime/Avibactam (13), Cefepime (2), Linezolid (3). Results: treatment was effective in all pt with no evidence of emerging resistance. Mean course duration was 13 days (6-30). In 21 cases (19.6%) mild side effects occurred: asymptomatic increase of liver enzymes (5.6%), nausea (5.6%), peripheral edema (3.7%), diarrhea (2.8%), hypokalemia (1.9%). One anaphylactic reaction occurred. Conclusions: ivFO proved to be effective in PEx in pwCF and pwNCFB even after repeated courses. Treatment was well tolerated, with fewer side effects than in previous literature, despite an older population.