IgG4-infiltrate in post-intubation tracheal stenosis: a call to interventional pulmonologist and thoracic surgeons

Background: Since December 2019, Sars-CoV2 infection has become a pandemic health emergency. The most severe manifestation of Covid-19 is acute respiratory distress syndrome requiring intensive care unit admission and mechanical ventilation. The most serious, although rare, complication of prolonged MV is post-intubation tracheal stenosis. We hypothesized that, in addition to recognized risk factors in Covid-19 patients, additional factors may promote airways injury. Methods: We analyzed data from 13 patients with PITS referred to our Thoracic Surgery Department from 2020 to 2022 divided in two groups: 8 ex-Covid-19 patients (in MV for ARDS during Sars-Cov2 positivity) and 5 non-Covid-19 patients (in MV for other reasons). Computer-tomography and bronchoscopy were performed to confirm diagnosis of PITS. Surgical treatment including tracheal resection and end-to-end anastomosis was performed in all patients. Tracheal samples were histologically analyzed to define the existence of any difference between the two groups. Results: The presence of total immunoglobulin G (IgG) and immunoglobulin G4 (IgG4) were tested. IgG infiltrate was present in both groups. IgG4-infiltrate was significantly represented in the tracheal sample of ex-Covid-19 patients and absent in the non-Covid-19 cohort of patients. Conclusions: It is suggested that Covid-19 patients have almost double the risk of developing tracheal injuries. This work supports the idea of a major predisposition for such injuries in Covid-19 patients due to a possible immune-mediated mechanism leading to aberrant and fibrotic wound healing following a trigger insult (in this case MV with oro-tracheal tube). In the near future an increasing incidence of PITS is expected. Interventional pulmonologist and thoracic surgeons might be called to deal with this possibility. Clarification of the physiopathology of PITS is needed to prevent excessive tracheal scarring following prolonged endotracheal intubation and recurrence after endoscopic and/or surgical treatment. Careful prevention, early detection and effective management of this life-threatening condition are warranted.