Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnoea and exercise capacity limitation.Objectives: the present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control.Methods: COPD patients with FEV1 <65% and plethysmographic functional residual capacity 120% of predicted were randomized to a double-blind, double-dummy, 12 week, parallel group, treatment with either BDP/F 400/24 \ub5g/day or FP/S 500/100\ub5g/day. Lung volumes were measured with full body plethysmography and dyspnoea was measured with transition dyspnoea index.Results: 18 patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnoea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F vs. FP/S. Conclusion: BDP/F extra-fine combination is effective in reducing air trapping and dyspnoea in COPD patients with lung hyperinflation

Rehabilitation of Difficult-to-Wean, Tracheostomized Patients Admitted to specialized unit: Retrospective Analyses Over 10-years.

Introduction: 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 de-scribes the characteristics and clinical outcomes of a large cohort of tracheostomized patients admitted to a specialized weaning unit over 10 years. Methods: We retrospectively analyzed da-ta 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 \u2013 CIRS) and the clinical se-verity (by the Simplified Acute Physiology Score \u2013 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 periods (2010-2014 and 2015-2019) subgroup analysis. Results: A to-tal of 180 patients were included in the analysis. Patients\u2019 anthropometry and preadmission clin-ical management in acute care hospital were similar across years, but the categories of underlying diagnosis changed (p&lt;0.001) (e.g. chronic obstructive pulmonary disease \u2013 COPD \u2013 decreased), while the level of comorbidities increased (p=0.003). Decannulation rate was 45.6%. CIRS and SAPS II at admission were both significant predictors of clinical outcomes. The proportion of pa-tients whose gain in BADL score increased 652 points decreased over time. Conclusions: This study confirms the importance of rehabilitation in the weaning units for the severely disabled subset of tracheostomized patients. Comorbidities and severity at admission are significantly as-sociated with rehabilitation outcomes at discharge

Early inspiratory effort assessment by esophageal manometry early predicts noninvasive ventilation outcome in de novo respiratory failure: a pilot study.

Rationale: The role of inspiratory effort has still to be determined as a potential predictors of non-invasive mechanical ventilation (NIV) failure in acute hypoxic de novo respiratory failure (AHRF). Objectives: We explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients. Methods: Thirty consecutive patients with AHRF admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal changes in esophageal (ΔPes) and dynamic transpulmonary pressure (ΔPL), expiratory tidal volume, and respiratory rate were recorded on admission and 2-4-12-24 hours after NIV start, and were tested for correlation with outcomes. Measurements and Main Results: ΔPes and ΔPes/ΔPL were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (n=18) compared to those who needed endotracheal intubation (n=12) [median=11 (IQR=8–15) cmH2O vs 31.5 (30–36) cmH2O, p&lt;0.0001] while other variables differed later. ΔPes was not related to other predictors of NIV failure at baseline. NIV-induced reduction in ΔPes of 10 cmH2O or more after 2 hours of treatment was strongly associated to avoidance of intubation, and represented the most accurate predictor of treatment success (OR=15, 95%CI 2.8-110, p=0.001, AUC=0.97, 95%CI 0.91–1, p&lt;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

Pretreatment rate of decay in forced vital capacity predicts long-term response to pirfenidone in patients with idiopathic pulmonary fibrosis.

Pirfenidone reduces functional decline and disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF). However, response to treatment is highly heterogeneous. In this study, we evaluated whether response to pirfenidone is influenced by the pre-treatment rate of forced vital capacity (FVC) decline. Fifty-seven IPF patients were categorized as rapid (RP) or slow progressors (SP) based on whether their FVC decline in the year preceding pirfenidone treatment was > or <10% predicted. Patients were followed-up every 6 months and up to 24 months following institution of pirfenidone treatment. In the entire population, pirfenidone reduced significantly the rate of FVC decline from 222 ml/yr to 68 ml/yr at 12 month (p<0.01) and 86 ml/yr at 24 month (p=0.04) follow-up. In RP, the reduction of FVC decline was evident at 6 months (706 ml/yr pre-treatment vs 35 ml/yr; p<0.01) and maintained, though to a lesser degree, at 12 (105 ml/yr; p< 0.01) and 24 months (125 ml/yr; p<0.02). Conversely, among SP the reduction in FVC decline was not significant at any of the time points analyzed. Pirfenidone reduces significantly the rate of FVC decline in patients with IPF. However, the beneficial effect is more pronounced and long-lasting in patients with rapidly progressive disease

Serial Ultrasound Assessment of Diaphragmatic Function and Clinical Outcome in Patients with Amyotrophic Lateral Sclerosis.

Background: Ultrasound (US) evaluation of the diaphragm may be a non-volitional useful tool in the clinical management of patients with ALS. Aim of the present study was then to evaluate the impact of serial assessment of ΔTmax index on clinical outcomes during the follow-up in these patients and to correlate non-volitional US indices and other volitional measures with these outcomes. Methods: A cohort of 39 consecutive patients with ALS was followed up to 24 months. At baseline and every 3-month spirometry (forced vital capacity-FVC), sniff inspiratory nasal pressure (SNIP), and US of the diaphragm (ΔTdi and ΔTmax) were recorded. These parameters were correlated with clinical outcomes (hypercapnia, nocturnal hypoventilation, NIV start in the following 6 month, and death within 1 year). Results: The occurrence of ΔTmax &gt;0.75 during follow-up increased the risk for NIV (HR=5.6, p=0.001) and death (HR=3.7, p=0.0001) compared with patients with stable lower values. The evidence of diaphragmatic dysfunction, i.e. ΔTmax &gt;0.75, occurs 3.2 month earlier than the onset of NIV. Moreover, ΔTmax &gt;0.75 correlated with onset of nocturnal hypoventilation, NIV initiation within 6 months, and death within 12 months, similarly to FVC &lt;50% predicted and better than other functional indices. Conclusions: Serial monitoring of diaphragmatic ΔTmax by US may be useful to predict initiation of NIV and death in patients with ALS. The occurrence of an abnormal ΔTmax value in the follow-up precedes the decision for starting NIV

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

The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated

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- AL 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. Conclusions- 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 (\u394P es ) and nasal (\u394P nos ) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods- From January 1 st , 2021 to September 1 st , 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 noninvasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 hours after starting NRS. Correlation between \u394P es and \u394P nos served as primary outcome. The effect of \u394P nos measurements on respiratory rate and \u394P es was also assessed. Results- \u394P es and \u394P nos were strongly correlated at admission (R 2 =0.88, p&lt;0.001) and 24 hours apart (R 2 =0.94, p&lt;0.001). The nasal plug insertion and the mouth closure required for \u394P nos measurement did not result in significant change of respiratory rate and \u394P es . The correlation between measures at 24 hours remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R 2 =0.79, p&lt;0.001] or non-invasive ventilation [R 2 =0.95, p&lt;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. \u394P nos might warrant further investigation as a measure of inspiratory effort in patients with ARF

Comparison between first and second wave of COVID-19 outbreak in older people. The COPE multicentre European observational cohort study

Background: Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise health care systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and 2 (W2). Methods: All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from thirteen hospitals, in W1 (February-June 2020) and W2 (October 2020-March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. Results: Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median [IQR], W2 = 79 [73-84]; W1 = 80 [74-86]; had a greater proportion of men (59.4% vs 53.0%); had lower 28-day mortality (29.1% vs 40.0%), compared to W1. For combined W1-W2 sample, W2 was independently associated with improved survival: time-to-mortality aHR= 0.78 (95%CI 0.65-0.93), 28-day mortality aOR = 0.80 (95%CI 0.62-1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95%CI 0.59-0.81). Patients in W2 were less frail, CFS (adjusted mean difference [aMD]=-0.50, 95%CI -0.81, -0.18), as well as presented with lower CRP (aMD=-22.52, 95%CI -32.00, -13.04). Conclusions: COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline