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.

Background: Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔP_es) and nasal (ΔP_nos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods: From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔP_es and ΔP_nos served as primary outcome. The effect of ΔP_nos measurements on respiratory rate and ΔP_es was also assessed. Results: ΔP_es and ΔP_nos were strongly correlated at admission (R² = 0.88, p < 0.001) and 24 h apart (R² = 0.94, p < 0.001). The nasal plug insertion and the mouth closure required for ΔP_nos measurement did not result in significant change of respiratory rate and ΔP_es. The correlation between measures at 24 h remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R² = 0.79, p < 0.001] or non-invasive ventilation [R² = 0.95, p < 0.001]). Conclusions: In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔP_nos might warrant further investigation as a measure of inspiratory effort in patients with ARF. Trial registration: NCT03826797. Registered October 2016.

The mechanisms of acute respiratory failure other than inflammation and complicating the SARS-CoV-2 infection are still far from being fully understood, thus challenging the management of COVID-19 patients in the critical care setting. In this unforeseen scenario, the role of an individual’s excessive spontaneous breathing may acquire critical importance, being one potential and important driver of lung injury and disease progression. The consequences of this acute lung damage may impair lung structure, forecasting the model of a fragile respiratory system. This perspective article aims to analyze the progression of injured lung phenotypes across the SARS-CoV-2 induced respiratory failure, pointing out the role of spontaneous breathing and also tackling the specific respiratory/ventilatory strategy required by the fragile lung type.

Background: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. Methods: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO₂/FiO₂ ratio). Three PEEP levels (zero = ZEEP, 4–8 cmH₂O = PEEP_LOW, and titrated to achieve positive end-expiratory transpulmonary pressure P_L,EE = PEEP_TITRATED) were used for measurements. Results: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median P_L,EE at ZEEP was − 4.3 [− 7.6– − 2.3] cmH₂O and lung elastance (E_L) 44 [40–51] cmH₂O/L. At PEEP_LOW, P_L,EE remained negative and E_L did not change (p = 0.995) versus ZEEP. At PEEP_TITRATED, P_L,EE increased to 0.8 [0.3–1.5] cmH₂O and E_L to 49 [43–59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEP_LOW, respectively). ΔP_L decreased at PEEP_LOW (p = 0.018) and increased at PEEP_TITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive P_L,EE did not result in significant changes in E_L and ΔP_L. Conclusions: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive P_L,EE significantly worsened lung mechanics.

Background: Sarcoidosis is a multisystem inflammatory disease characterized by the immune-mediated formation of non-necrotizing epithelioid granulomas. Several commonly used medications can induce similar granulomatous reactions, known as drug-induced sarcoid-like reactions (DISRs), which closely mimic sarcoidosis. Despite their specificity in targeting molecular pathways, certain therapies—particularly targeted treatments—have increasingly been linked to DISRs. Methods: This narrative review was based on a PubMed search using the terms “SARCOID LIKE REACTION” and “DRUG”. A cross-check was performed with “SARCOID” combined with each identified drug to identify misclassified cases. Drugs with limited evidence or weak pathogenetic plausibility were excluded, leaving only molecularly targeted therapies for consideration. Sources included case reports, case series, and reviews selected based on their clinical and scientific relevance, without any restrictions on time or language. Results: In light of the available data, five main pharmacological groups were found to be associated to DISR: immune checkpoint inhibitors, TNF-α antagonists, BRAF inhibitors, monoclonal antibodies, and miscellaneous agents. Each group has distinct mechanisms of action and clinical indications, which likely affect the frequency, presentation, and timing of DISRs. Conclusions: Diagnosing DISRs is challenging, and a structured approach is crucial for differentiating them from other conditions. To support clinicians, we propose a diagnostic algorithm to guide decision-making in suspected cases. Management should be individualized, as most DISRs either resolve spontaneously or improve after the discontinuation of the causative drug. Important factors influencing therapeutic decisions include the severity of the underlying disease, the availability of alternative treatments, and the extent of DISR manifestations.