Riccardo Fantini

Non-invasive respiratory support, namely, non-invasive ventilation, continuous positive airway pressure, and high-flow nasal cannula, has been increasingly used worldwide to treat acute hypoxemic respiratory failure, giving the benefits of keeping spontaneous breathing preserved. In this scenario, monitoring and controlling respiratory drive could be helpful to avoid patient self-inflicted lung injury and promptly identify those patients that require an upgrade to invasive mechanical ventilation. In this review, we first describe the physiological components affecting respiratory drive to outline the risks associated with its hyperactivation. Further, we analyze and compare the leading strategies implemented for respiratory drive monitoring and discuss the sedative drugs and the non-pharmacological approaches used to modulate respiratory drive during non-invasive respiratory support. Refining the available techniques and rethinking our therapeutic and monitoring targets can help critical care physicians develop a personalized and minimally invasive approach. Graphical abstract

High flow nasal oxygen (HFNO) is recommended as a first-line respiratory support during acute hypoxic respiratory failure (AHRF) and represents a proportionate treatment option for patients with do not intubate (DNI) orders. The aim of the study is to assess the effect of HFNO on inspiratory effort as assessed by esophageal manometry in a population of DNI patients suffering from AHRF. Patients with AHRF and DNI orders admitted to Respiratory intermediate Care Unit between January 1st, 2018 and May 31st, 2023 to receive HFNO and subjected to esophageal manometry were enrolled. Esophageal pressure swing (ΔP_es), clinical variables before and after 2 h of HFNO and clinical outcome (including HFNO failure) were collected and compared as appropriate. The change in physiological and clinical parameters according to the intensity of baseline breathing effort was assessed and the correlation between baseline ΔP_es values and the relative change in breathing effort and clinical variables after 2 h of HFNO was explored. Eighty-two consecutive patients were enrolled according to sample size calculation. Two hours after HFNO start, patients presented significant improvement in ΔP_es (12 VS 16 cmH₂O, p < 0.0001), respiratory rate (RR) (22 VS 28 bpm, p < 0.0001), PaO₂/FiO₂ (133 VS 126 mmHg, p < 0.0001), Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, (4 VS 6, p < 0.0001), Respiratory rate Oxygenation (ROX) index (8.5 VS 6.1, p < 0.0001) and BORG (1 VS 4, p < 000.1). Patients with baseline ΔP_es below 20 cmH₂O where those who improved all the explored variables, while patients with baseline ΔP_es above 30 cmH₂O did not report significant changes in physiological or clinical features. A significant correlation was found between baseline ΔP_es values and after 2 h of HFNO (R² = 0.9, p < 0.0001). ΔP_es change 2 h after HFNO significantly correlated with change in BORG (p < 0.0001), ROX index (p < 0.0001), HACOR score (p < 0.001) and RR (p < 0.001). In DNI patients with AHRF, HFNO was effective in reducing breathing effort and improving respiratory and clinical variables only for those patients with not excessive inspiratory effort.

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.

This retrospective cohort study was conducted in two teaching hospitals over a 3-monthperiod (March 2010-June 2020) comparing severe and critical COVID-19 patients admitted to Respiratory Intensive Care Unit for non-invasive respiratory support (NRS) and subjected to awake prone position (PP) with those receiving standard care (SC). Primary outcome was endotracheal intubation (ETI) rate. In-hospital mortality, time to ETI, tracheostomy, length of RICU and hospital stay served as secondary outcomes. Risk factors associated to ETI among PP patients were also investigated. A total of 114 patients were included, 76 in the SC and 38 in the PP group. Unadjusted Kaplan-Meier estimates showed greater effect of PP compared to SC on ETI rate (HR = 0.45 95%CI [0.2-0.9], p = 0.02) even after adjustment for baseline confounders (HR = 0.59 95%CI[0.3-0.94], p = 0.03). After stratification according to non-invasive respiratory support, PP showed greater significant benefit for those on high flow nasal cannulae (HR = 0.34 95%CI[0.12-0.84], p = 0.04). Compared to SC, PP patients also showed a favorable difference in terms of days free from respiratory support, length of RICU and hospital stay while mortality and tracheostomy rate were not significantly different. Prone positioning in awake and spontaneously breathing Covid-19 patients is feasible and associated with a reduction of intubation rate, especially in those patients undergoing HFNC. Although our results are intriguing, further randomized controlled trials are needed to answer all the open questions remaining pending about the real efficacy of PP in this setting.

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.

Rehabilitation outcomes of difficult-to-wean tracheostomized patients have been reported in relatively small case studies and described for a limited time span. This study describes the characteristics and clinical outcomes of a large cohort of tracheostomized patients admitted to a specialized weaning unit over 10 years. We retrospectively analyzed data collected from January 2010 to December 2019 on difficult-to-wean tracheostomized patients who underwent comprehensive rehabilitation. Clinical characteristics collected at admission were the level of comorbidity (by the Cumulative Illness Rating Scale—CIRS) and the clinical severity (by the Simplified Acute Physiology Score—SAPS II). The proportions of patients weaned, decannulated, and able to walk; the change in autonomy level according to the Bristol Activities of Daily Living (BADL) Scale; and the setting of hospital discharge was assessed and compared in a consecutive 5-year time period (2010–2014 and 2015–2019) subgroup analysis. A total of 180 patients were included in the analysis. Patient anthropometry and preadmission clinical management in acute care hospitals were similar across years, but the categories of underlying diagnosis changed (p < 0.001) (e.g., chronic obstructive pulmonary disease—COPD—decreased), while the level of comorbidities increased (p = 0.003). The decannulation rate was 45.6%. CIRS and SAPS II at admission were both significant predictors of clinical outcomes. The proportion of patients whose gain in BADL score increased ≥ 2 points decreased over time. This study confirms the importance of rehabilitation in weaning units for the severely disabled subset of tracheostomized patients. Comorbidities and severity at admission are significantly associated with rehabilitation outcomes at discharge.

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.

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress–strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.