PMID- 35269565 OWN - NLM STAT- MEDLINE DCOM- 20220325 LR - 20220325 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 5 DP - 2022 Feb 22 TI - Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults. LID - 10.3390/ijms23052421 [doi] LID - 2421 AB - Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS. FAU - Marchioni, Alessandro AU - Marchioni A AUID- ORCID: 0000-0003-3720-3517 AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Tonelli, Roberto AU - Tonelli R AUID- ORCID: 0000-0002-6202-0758 AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. AD - Clinical and Experimental Medicine PhD Program, University of Modena Reggio Emilia, 41121 Modena, Italy. FAU - Andreani, Alessandro AU - Andreani A AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Cappiello, Gaia Francesca AU - Cappiello GF AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Fermi, Matteo AU - Fermi M AD - Otolaryngology Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - Trentacosti, Fabiana AU - Trentacosti F AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Castaniere, Ivana AU - Castaniere I AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. AD - Otolaryngology Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - Fantini, Riccardo AU - Fantini R AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Tabbi, Luca AU - Tabbi L AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Andrisani, Dario AU - Andrisani D AUID- ORCID: 0000-0003-3860-0063 AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. AD - Clinical and Experimental Medicine PhD Program, University of Modena Reggio Emilia, 41121 Modena, Italy. FAU - Gozzi, Filippo AU - Gozzi F AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. AD - Clinical and Experimental Medicine PhD Program, University of Modena Reggio Emilia, 41121 Modena, Italy. FAU - Bruzzi, Giulia AU - Bruzzi G AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Manicardi, Linda AU - Manicardi L AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Moretti, Antonio AU - Moretti A AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Baroncini, Serena AU - Baroncini S AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Samarelli, Anna Valeria AU - Samarelli AV AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. FAU - Pinelli, Massimo AU - Pinelli M AD - Plastic Surgery Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - De Santis, Giorgio AU - De Santis G AD - Plastic Surgery Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - Stefani, Alessandro AU - Stefani A AD - Thoracic Surgery Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - Marchioni, Daniele AU - Marchioni D AD - Otolaryngology Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - Mattioli, Francesco AU - Mattioli F AD - Otolaryngology Unit, University Hospital of Modena, 41121 Modena, Italy. FAU - Clini, Enrico AU - Clini E AUID- ORCID: 0000-0002-1515-5094 AD - Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University of Modena Reggio Emilia, University Hospital of Modena, 41121 Modena, Italy. LA - eng PT - Journal Article PT - Review DEP - 20220222 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Intercellular Signaling Peptides and Proteins) SB - IM MH - Biomarkers/*metabolism MH - Biomechanical Phenomena MH - Cytokines/metabolism MH - Genetic Predisposition to Disease MH - Humans MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Laryngostenosis/genetics/metabolism/*pathology MH - Mechanotransduction, Cellular MH - Tracheal Stenosis/genetics/metabolism/*pathology PMC - PMC8910114 OTO - NOTNLM OT - granulomatosis with polyangiitis OT - relapsing polychondritis OT - subglottic stenosis OT - tracheal stenosis OT - tracheostomy OT - web-like stenosis COIS- The authors have no competing interests with any organization or entity with a financial interest in competition with the subject, matter, or materials discussed in the manuscript. EDAT- 2022/03/11 06:00 MHDA- 2022/03/26 06:00 PMCR- 2022/02/22 CRDT- 2022/03/10 15:34 PHST- 2022/02/02 00:00 [received] PHST- 2022/02/16 00:00 [revised] PHST- 2022/02/21 00:00 [accepted] PHST- 2022/03/10 15:34 [entrez] PHST- 2022/03/11 06:00 [pubmed] PHST- 2022/03/26 06:00 [medline] PHST- 2022/02/22 00:00 [pmc-release] AID - ijms23052421 [pii] AID - ijms-23-02421 [pii] AID - 10.3390/ijms23052421 [doi] PST - epublish SO - Int J Mol Sci. 2022 Feb 22;23(5):2421. doi: 10.3390/ijms23052421.