Risk Factors for Pulmonary Air Leak and Clinical Prognosis in Patients With COVID-19 Related Acute Respiratory Failure: A Retrospective Matched Control Study.

Background: The role of excessive inspiratory effort in promoting alveolar and pleural rupture resulting in air leak (AL) in patients with SARS-CoV-2 induced acute respiratory failure (ARF) while on spontaneous breathing is undetermined. Methods: Among all patients with COVID-19 related ARF admitted to a respiratory intensive care unit (RICU) and receiving non-invasive respiratory support, those developing an AL were and matched 1:1 [by means of PaO2/FiO2 ratio, age, body mass index-BMI and subsequent organ failure assessment (SOFA)] with a comparable population who did not (NAL group). Esophageal pressure (ΔPes) and dynamic transpulmonary pressure (ΔPL) swings were compared between groups. Risk factors affecting AL onset were evaluated. The composite outcome of ventilator-free-days (VFD) at day 28 (including ETI, mortality, tracheostomy) was compared between groups. Results: Air leak and NAL groups (n = 28) showed similar ΔPes, whereas AL had higher ΔPL (20 [16-21] and 17 [11-20], p = 0.01, respectively). Higher ΔPL (OR = 1.5 95%CI[1-1.8], p = 0.01), positive end-expiratory pressure (OR = 2.4 95%CI[1.2-5.9], p = 0.04) and pressure support (OR = 1.8 95%CI[1.1-3.5], p = 0.03), D-dimer on admission (OR = 2.1 95%CI[1.3-9.8], p = 0.03), and features suggestive of consolidation on computed tomography scan (OR = 3.8 95%CI[1.1-15], p = 0.04) were all significantly associated with AL. A lower VFD score resulted in a higher risk (HR = 3.7 95%CI [1.2-11.3], p = 0.01) in the AL group compared with NAL. RICU stay and 90-day mortality were also higher in the AL group compared with NAL. Conclusion: In spontaneously breathing patients with COVID-19 related ARF, higher levels of ΔPL, blood D-dimer, NIV delivery pressures and a consolidative lung pattern were associated with AL onset.

Nasal pressure swings as the measure of inspiratory effort in spontaneously breathing patients with de novo acute respiratory failure.

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 (ΔPes) and nasal (ΔPnos) 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 ΔPes and ΔPnos served as primary outcome. The effect of ΔPnos measurements on respiratory rate and ΔPes was also assessed. RESULTS: ΔPes and ΔPnos 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 ΔPnos measurement did not result in significant change of respiratory rate and ΔPes. 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. ΔPnos might warrant further investigation as a measure of inspiratory effort in patients with ARF. TRIAL REGISTRATION: NCT03826797 . Registered October 2016.

Differences between Acute Exacerbations of Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases.

Interstitial lung diseases (ILDs) comprise a wide group of pulmonary parenchymal disorders. These patients may experience acute respiratory deteriorations of their respiratory condition, termed "acute exacerbation" (AE). The incidence of AE-ILD seems to be lower than idiopathic pulmonary fibrosis (IPF), but prognosis and prognostic factors are largely unrecognized. We retrospectively analyzed a cohort of 158 consecutive adult patients hospitalized for AE-ILD in two Italian university hospitals from 2009 to 2016. Patients included in the analysis were divided into two groups: non-IPF (62%) and IPF (38%). Among ILDs included in the non-IPF group, the most frequent diagnoses were non-specific interstitial pneumonia (NSIP) (42%) and connective tissue disease (CTD)-ILD (20%). Mortality during hospitalization was significantly different between the two groups: 19% in the non-IPF group and 43% in the IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers, such as neutrophilia on the differential blood cell count (HR 1.02 (CI 1.01-1.04)), the presence of pulmonary hypertension (HR 1.85 (CI 1.17-2.92)), and the diagnosis of IPF (HR 2.31 (CI 1.55-3.46)), resulted in negative prognostic factors in our analysis. Otherwise, lymphocytosis on the differential count seemed to act as a protective prognostic factor (OR 0.938 (CI 0.884-0.995)). Further prospective, large-scale, real-world data are needed to support and confirm the impact of our findings.

Endobronchial valve positioning for alveolar-pleural fistula following ICU management complicating COVID-19 pneumonia.

BACKGROUND: The main clinical consequences of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection are pneumonia and respiratory failure even requiring mechanical ventilation. In this context, the lung parenchyma is highly prone to ventilator-related injury, with pneumothorax and persistent air leak as the most serious adverse events. So far, endobronchial valve (EBV) positioning has proved efficacious in treating air leaks with a high success rate. CASE PRESENTATION: We report, for the first time, two cases of patients affected by SARS-CoV-2-related pneumonia complicated with bacterial super-infection, experiencing pneumothorax and persistent air leaks after invasive mechanical ventilation. Despite the severity of respiratory failure both patients underwent rigid interventional bronchoscopy and were successfully treated through EBV positioning. CONCLUSIONS: Persistent air leaks may result from lung tissue damage due to a complex interaction between inflammation and ventilator-related injury (VILI), especially in the advanced stages of ARDS. EBV positioning seems to be a feasible and effective minimally invasive therapeutic option for treating this subset of patients.

Early Inspiratory Effort Assessment by Esophageal Manometry Predicts Noninvasive Ventilation Outcome in De Novo Respiratory Failure. A Pilot Study.

Rationale: The role of inspiratory effort still has to be determined as a potential predictor of noninvasive mechanical ventilation (NIV) failure in acute hypoxic de novo respiratory failure.Objectives: To explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients.Methods: Thirty consecutive patients with acute hypoxic de novo respiratory failure admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal change in esophageal pressure (ΔPes), tidal change in dynamic transpulmonary pressure (ΔPl), expiratory Vt, and respiratory rate were recorded on admission and 2-4 to 12-24 hours after NIV start and were tested for correlation with outcomes.Measurements and Main Results: ΔPes and ΔPes/ΔPl ratio were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (n = 18) compared with those who needed endotracheal intubation (n = 12) (median [interquartile range], 11 [8-15] cm H2O vs. 31.5 [30-36] cm H2O; P < 0.0001), whereas other variables differed later. ΔPes was not related to other predictors of NIV failure at baseline. NIV-induced reduction in ΔPes of 10 cm H2O or more after 2 hours of treatment was strongly associated with avoidance of intubation and represented the most accurate predictor of treatment success (odds ratio, 15; 95% confidence interval, 2.8-110; P = 0.001 and area under the curve, 0.97; 95% confidence interval, 0.91-1; P < 0.0001).Conclusions: The magnitude of inspiratory effort relief as assessed by ΔPes variation within the first 2 hours of NIV was an early and accurate predictor of NIV outcome at 24 hours.Clinical trial registered with www.clinicaltrials.gov (NCT03826797).

Ventilatory support and mechanical properties of the fibrotic lung acting as a "squishy ball".

Protective ventilation is the cornerstone of treatment of patients with the acute respiratory distress syndrome (ARDS); however, no studies have yet established the best ventilatory strategy to adopt when patients with acute exacerbation of interstitial lung disease (AE-ILD) are admitted to the intensive care unit. Due to the severe impairment of the respiratory mechanics, the fibrotic lung is at high risk of developing ventilator-induced lung injury, regardless of the lung fibrosis etiology. The purpose of this review is to analyze the effects of mechanical ventilation in AE-ILD and to increase the knowledge on the characteristics of fibrotic lung during artificial ventilation, introducing the concept of "squishy ball lung". The role of positive end-expiratory pressure is discussed, proposing a "lung resting strategy" as opposed to the "open lung approach". The review also discusses the practical management of AE-ILD patients discussing illustrative clinical cases.

Serial ultrasound assessment of diaphragmatic function and clinical outcome in patients with amyotrophic lateral sclerosis.

BACKGROUND: Diaphragmatic assessment by ultrasound (US) is a non-invasive and useful method in the clinical management of patients with Amyotrophic Lateral Sclerosis (ALS). The aim of our observational study was to evaluate the impact of serial assessment of the diaphragmatic function by US on long-term outcomes in a series of patients suffering from ALS and to correlate US indices of diaphragmatic function and respiratory function tests with these outcomes. METHODS: A cohort of 39 consecutive patients has been followed up to 24 months. Both lung volume (forced vital capacity, FVC) and diaphragmatic pressure generating capacity (by sniff inspiratory nasal pressure (SNIP) and by both US thickening fraction, ΔTdi, and the ratio of the thickening fraction between tidal volume and maximal lung capacity, ΔTmax) were recorded at baseline and every 3 months. Parameters were then correlated with outcomes (nocturnal hypoventilation, daily hypercapnia, start of ventilatory support (NIV), and death at 1 year) over time. RESULTS: The occurrence of ΔTmax > 0.75 increased the risk to start NIV (HR = 5.6, p = 0.001) and to die (HR = 3.7, p = 0.0001) compared with patients maintaining lower values. Moreover, compared with the occurrence of FVC < 50% of predicted, ΔTmax > 0.75 appeared slightly better correlated with NIV commencement within 6 months. CONCLUSIONS: Serial diaphragmatic assessment by ultrasound is a useful and accurate method to predict the initiation of NIV earlier in patients with ALS.