Decrease of haemoconcentration reliably detects hydrostatic pulmonary oedema in dyspnoeic patients in the emergency department - a machine learning approach.

BACKGROUND: Haemoglobin variation (ΔHb) induced by fluid transfer through the intestitium has been proposed as a useful tool for detecting hydrostatic pulmonary oedema (HPO). However, its use in the emergency department (ED) setting still needs to be determined. METHODS: In this observational retrospective monocentric study, ED patients admitted for acute dyspnoea were enrolled. Hb values were recorded both at ED presentation (T0) and after 4 to 8 h (T1). ΔHb between T1 and T0 (ΔHbT1-T0) was calculated as absolute and relative value. Two investigators, unaware of Hb values, defined the cause of dyspnoea as HPO and non-HPO. ΔHbT1-T0 ability to detect HPO was evaluated. A machine learning approach was used to develop a predictive tool for HPO, by considering the ability of ΔHb as covariate, together with baseline patient characteristics. RESULTS: Seven-hundred-and-six dyspnoeic patients (203 HPO and 503 non-HPO) were enrolled over 19 months. Hb levels were significantly different between HPO and non-HPO patients both at T0 and T1 (p < 0.001). ΔHbT1-T0 were more pronounced in HPO than non-HPO patients, both as relative (-8.2 [-11.2 to -5.6] vs. 0.6 [-2.1 to 3.3] %) and absolute (-1.0 [-1.4 to -0.8] vs. 0.1 [-0.3 to 0.4] g/dL) values (p < 0.001). A relative ΔHbT1-T0 of -5% detected HPO with an area under the receiver operating characteristic curve (AUROC) of 0.901 [0.896-0.906]. Among the considered models, Gradient Boosting Machine showed excellent predictive ability in identifying HPO patients and was used to create a web-based application. ΔHbT1-T0 was confirmed as the most important covariate for HPO prediction. CONCLUSIONS: ΔHbT1-T0 in patients admitted for acute dyspnoea reliably identifies HPO in the ED setting. The machine learning predictive tool may represent a performing and clinically handy tool for confirming HPO.

The Role of Medical Thoracoscopy with Talc Poudrage in Spontaneous, Iatrogenic, and Traumatic Pneumothorax: A Prolonged Experience of a Tertiary Care Center.

INTRODUCTION: Medical thoracoscopy is a minimally invasive and safe procedure mostly performed for unexplained exudative pleural effusions but may be considered for pneumothorax (PNX). METHODS: This retrospective study included participants affected by PNX who underwent medical thoracoscopy with talc poudrage at a single academic hospital from 2008 to 2021. The primary endpoint was the observation of complete radiographical lung re-expansion and absence of air supply from the chest drain within 7 days of medical thoracoscopy. The secondary endpoint was achieving no recurrence of ipsilateral PNX at 24 months post-discharge. RESULTS: A total of 95 patients affected by primary spontaneous PNX (PSP), secondary spontaneous PNX (SSP), iatrogenic, and traumatic PNX were enrolled. An additional procedure was required by 17.89% of patients, and only one patient with SSP required subsequent surgery. Recurrence of PNX occurred on the same side within 24 months after discharge in 9.47% of patients, with a median time to recurrence of 13.5 months. The PSP group was significantly more likely to achieve the primary endpoint. Pleural morphology was significantly associated with reaching the primary endpoint, while receiving a cumulative dose of talc greater than or equal to 4 g during hospitalization was associated with a lower risk of meeting it. Receiving a cumulative dose of talc greater than or equal to 4 g led in all cases to the achievement of the secondary endpoint. Patients with iatrogenic and traumatic PNX had an excellent prognosis in both the short- and long-term evaluation. CONCLUSION: Medical thoracoscopy is an effective procedure for treating PNX in the acute setting in selected cases while preventing long-term relapses. Large prospective clinical studies are needed to support and better define the role of medical thoracoscopy in current clinical practice.

Exploring the efficacy and advancements of medical pleurodesis: a comprehensive review of current research.

This narrative review aims to provide an overview of medical pleurodesis techniques, and their indications and potential adverse effects. Pleurodesis is a procedure performed with the aim of obliterating the pleural space. It has indications in the management of both malignant and benign pleural effusions and pneumothorax. Various nonsurgical techniques exist to perform pleurodesis. The scope of this work is to review the different nonsurgical techniques and their indications. This narrative review was performed checking scientific databases for medical literature, focusing especially on the data derived from randomised controlled trials. Pleurodesis is an effective method to manage pleural effusions and pneumothorax, and minimally invasive techniques are now frequently used with good results. Further research is needed to assess the efficacy of new treatments and the possibility of using different techniques in association.

QuantiFERON CMV Test and CMV Serostatus in Lung Transplant: Stratification Risk for Infection, Chronic and Acute Allograft Rejection.

The QuantiFERON CMV (QCMV) test evaluates specific adaptive immune system activity against CMV by measuring IFN-γ released by activated CD8+ T lymphocytes. We aimed to evaluate the QCMV test as a predictive tool for CMV manifestations and acute or chronic lung allograft rejection (AR and CLAD) in lung transplant (LTx) patients. A total of 73 patients were divided into four groups based on donor and recipient (D/R) serology for CMV and QCMV assay: group A low-risk for CMV infection and disease (D-/R-); group B and C at intermediate-risk (R+), group B with non-reactive QCMV and group C with reactive QCMV; group D at high-risk (D+/R-). Group D patients experienced higher viral replication; no differences were observed among R+ patients of groups B and C. D+/R- patients had a higher number of AR events and group C presented a lower incidence of AR. Prevalence of CLAD at 24 months was higher in group B with a higher risk of CLAD development (OR 6.33). The QCMV test allows us to identify R+ non-reactive QCMV population as the most exposed to onset of CLAD. This population had a higher, although non-significant, susceptibility to AR compared to the R+ population with reactive QCMV.

Pneumomediastinum in COVID-19: Risk factors and outcomes from a multicentre case-control study.

BACKGROUND: An increased incidence of pneumomediastinum has been observed among patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. The study aimed to identify risk factors for COVID-19-associated pneumomediastinum and investigate the impact of pneumomediastinum on clinical outcomes. METHODS: In this multicentre retrospective case-control study, we included consecutive patients with COVID-19 pneumonia and pneumomediastinum hospitalized from March 2020 to July 2020 at ten centres; then, we identified a similarly sized control group of consecutive patients hospitalized with COVID-19 pneumonia and respiratory failure who did not develop pneumomediastinum during the same period. Clinical, laboratory, and radiological characteristics, as well as respiratory support and outcomes, were collected and compared between the two groups. Risk factors of pneumomediastinum were assessed by multivariable logistic analysis. RESULTS: Overall 139 patients with pneumomediastinum and 153 without pneumomediastinum were analysed. Lung involvement ≥75 %, consolidations, body mass index (BMI) < 22 kg/m2, C-reactive protein (CRP) > 150 mg/L, D-dimer >3000 ng/mL FEUs, and smoking exposure >20 pack-year were all independently correlated with the occurrence of pneumomediastinum. Patients with pneumomediastinum had a longer hospital stay (mean ± SD 31.2 ± 20.2 days vs 19.6 ± 14.2, p < 0.001), higher intubation rate (73/139, 52.5 % vs 27/153, 17.6 %, p < 0.001), and in-hospital mortality (68/139, 48.9 % vs 36/153, 23.5 %, p < 0.001) compared to controls. CONCLUSIONS: Extensive lung parenchyma involvement, consolidations, low BMI, high inflammatory markers, and tobacco exposure are associated with a greater risk of pneumomediastinum in COVID-19 pneumonia. This complication significantly worsens the outcomes.

Beyond diagnosis: a narrative review of the evolving therapeutic role of medical thoracoscopy in the management of pleural diseases.

Background and Objective: Medical thoracoscopy (MT) is an endoscopic technique performed by interventional pulmonologists with a favorable safety profile and few contraindications, providing diagnostic and therapeutic intervention in a single sitting. This narrative review was designed to summarize the therapeutic role of MT based on the latest results from the available literature. Methods: Pertinent literature published in English, relative to human studies, between 2010-2022 was searched in Medline/PubMed and Cochrane databases. Publications regarded as relevant were considered for inclusion in this review; additional references were added based on the authors' knowledge and judgment. The review considered population studies, meta-analyses, case series, and case reports. Key Content and Findings: MT has mostly been described and is currently used globally in the diagnostic approach to exudative pleural effusion of undetermined origin. Carefully evaluating the literature, it is clear that there is initial evidence to support the use of MT in the therapeutic approach of malignant pleural effusion, pneumothorax, empyema, and less frequently hemothorax and foreign body retrieval. Conclusions: MT is an effective procedure for treating the clinical entities presented in this document; it must be carried out in selected patients, managed in centers with high procedural expertise. Further evidence is needed to assess the optimal indications and appropriate patients' profiles for therapeutic MT. The endpoints of length of hospital stay, surgical referral, complications and mortality will have to be considered in future studies to validate it as a therapeutic intervention to be applied globally.

Herpes Virus Infection in Lung Transplantation: Diagnosis, Treatment and Prevention Strategies.

Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.

Environmental Impact of Bronchoscopy: Analysis of Waste Mass and Recyclability of Bronchoscopic Equipment and Consumables.

BACKGROUND: Greenhouse gases (GHGs) are significant contributors to climate change, and CO2 equivalent (CO2-e) is measured to compare emissions from GHGs. The healthcare sector contributes 4.4% of global CO2-e emissions, mainly with energy consumption and, in lesser extent, waste production. In this regard, bronchoscopy procedures produce a large amount of waste and are responsible for a significant consumption of energy. OBJECTIVE: We aimed at quantifying the impact on waste mass production, energy consumption, and recyclability of bronchoscopic procedures. METHODS: We conducted a prospective single-centre observational study; for each type of procedure (performed with either reusable or single-use instruments), the number of items used, their weight, and recyclability were evaluated, as well as the material of which recyclable waste was made of. We then calculated the total amount of waste produced, its recyclability, energy consumption, and CO2-e produced over 10 days of activity in our Interventional Pulmonology Unit. RESULTS: Sixty procedures generated 61,928 g of waste, of which only 15.8% was potentially recyclable. Single-use instruments generated nearly twofold more recyclable waste than reusable ones, 80% during the procedure phase. Reusable instruments generated 45% of waste during the reprocessing phase, of which 50% was recyclable. The recyclable material was totally composed of paper and plastic. During 10 days of activity, we consumed 64 kWh and produced more than 67 kg of CO2-e due to non-recyclable waste and energy consumption. CONCLUSIONS: Our results confirm the compelling need to recycle as many materials as possible, even if the amount of recyclable waste is limited. In this respect, official documents issued by international societies are urgently needed to align our activity with climate requirements and improve the sustainability of our work.

A Review: The Potential Involvement of Growth Arrest-Specific 6 and Its Receptors in the Pathogenesis of Lung Damage and in Coronavirus Disease 2019.

The tyrosine kinase receptors of the TAM family-Tyro3, Axl and Mer-and their main ligand Gas6 (growth arrest-specific 6) have been implicated in several human diseases, having a particularly important role in the regulation of innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells and this mechanism has been exploited by viruses for cell entry and infection. Coronavirus disease 2019 (COVID-19) is a multi-systemic disease, but the lungs are particularly affected during the acute phase and some patients may suffer persistent lung damage. Among the manifestations of the disease, fibrotic abnormalities have been observed among the survivors of COVID-19. The mechanisms of COVID-related fibrosis remain elusive, even though some parallels may be drawn with other fibrotic diseases, such as idiopathic pulmonary fibrosis. Due to the still limited number of scientific studies addressing this question, in this review we aimed to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms underlying COVID-19, with emphasis on the development of a fibrotic phenotype.

Endobronchial ultrasound: a pictorial essay.

BACKGROUND AND AIM: endobronchial ultrasound has gained widespread popularity in the last decade, becoming the primary technique for minimally invasive evaluation of the mediastinum and staging of lung cancer. Several tertiary and quaternary care institutes use this method, performed by trained and accredited specialists. Its main indications are (I) diagnosis and staging of lung cancer, (II) mediastinal lymphadenopathy diagnosis (III) sampling peripheral pulmonary lesions. CONCLUSIONS: this manuscript aims to describe the operational potential of both convex endobronchial ultrasound probe and radial endobronchial ultrasound probe technology, focusing on lung cancer. This narrative review is complemented with by the description of peculiar clinical cases in which endobronchial ultrasound played a pivotal role in reaching the diagnosis.

Measure of lung dielectric proprieties in patients with Idiopathic Pulmonary Fibrosis: correlation with clinical, radiological and pulmonary functional parameters.

BACKGROUND: Dielectric properties of biological tissues are biophysical parameters; in lung they change with amount of air, blood and parenchyma. Remote Dielectric Sensing (ReDS™) technology measures dielectric properties of lung tissues quantifying the content of fluids inside the scan volume. We aimed to evaluate the reliability of ReDS™ measure in Idiopathic Pulmonary Fibrosis (IPF) patients and in healthy volunteers, and to investigate the correlation of ReDS™ score with clinical, radiological and functional parameters. METHODS: We conducted a prospective observational study, including 52 patients with diagnosis of IPF and 17 healthy volunteers; for each patient we recorded: complete functional evaluation, dyspnoea score (mMRC scale), Usual Interstitial Pneumonia (UIP) Computed Tomography (CT) pattern (UIP definite or probable) and ReDS™ measure (expressed in %). RESULTS: ReDS™ measure was reported as correct both in patients and controls, the firsts with higher scores (33.8% vs 29.1%, p = 0.003). In IPF patients we observed a significant inverse correlation with ReDS™ score and Forced Vital Capacity (FVC), Vital Capacity (VC) and Total Lung Capacity (TLC) measures and, when we considered only patients with UIP definite CT pattern, the correlation was inverse with FVC, VC, TLC, DLCO. In IPF patients the higher was mMRC dyspnoea index, the higher was ReDS™ score. No significant correlations were observed between ReDS™ score and functional parameters in healthy controls. DISCUSSION: We demonstrated a correlation of ReDS™ scores with some functional (mainly indicative or diagnostic for restriction) and clinical parameters in IPF patients; the score was correlated with density of tissues possibly quantifying tissue fibrosis in IPF patients.

Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Idiopathic Pulmonary Fibrosis and Post-COVID-19 Lung Fibrosis: Links and Risks.

Idiopathic pulmonary fibrosis (IPF) is considered the paradigmatic example of chronic progressive fibrosing disease; IPF does not result from a primary immunopathogenic mechanism, but immune cells play a complex role in orchestrating the fibrosing response. These cells are activated by pathogen-associated or danger-associated molecular patterns generating pro-fibrotic pathways or downregulating anti-fibrotic agents. Post-COVID pulmonary fibrosis (PCPF) is an emerging clinical entity, following SARS-CoV-2 infection; it shares many clinical, pathological, and immune features with IPF. Similarities between IPF and PCPF can be found in intra- and extracellular physiopathological pro-fibrotic processes, genetic signatures, as well as in the response to antifibrotic treatments. Moreover, SARS-CoV-2 infection can be a cause of acute exacerbation of IPF (AE-IPF), which can negatively impact on IPF patients' prognosis. In this narrative review, we explore the pathophysiological aspects of IPF, with particular attention given to the intracellular signaling involved in the generation of fibrosis in IPF and during the SARS-CoV-2 infection, and the similarities between IPF and PCPF. Finally, we focus on COVID-19 and IPF in clinical practice.

Interventional pulmonology techniques in lung transplantation.

Lung transplantation is a key therapeutic option for several end-stage lung diseases. Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications. We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation. We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications. The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia). First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation. High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.

Combining three-dimensional fluoroscopy guide system with single-use bronchoscopes for diagnosis of peripheral lesions: First two cases.

Pulmonary Peripheral Lesions (PPLs) diagnosis is usually performed using a guidance system in combination with bronchoscopes and diagnostic tools. We report two cases of PPLs sampling procedures combining the use of the single-use bronchoscope Ambu aScope 5 Broncho and CIOS 3D Spin Mobile (Siemens Healthineers) fluoroscopy system. A 69-year-old-female was found to have a lesion located in right B6 segment and a 73-year-old-male with a mass in the upper right lobe. We used for both cases a single-use bronchoscope to reach the correct area and the fluoroscopy system to guide peripheral transbronchial aspiration needle (TBNA) sampling. After the confirmation of the correct location of the TBNA tool, the sampling was performed. Rapid onsite evaluation (ROSE) confirmed the adequacy of the sample for molecular analysis and the final diagnosis. Thus, the use of ever-new disposable bronchoscopes for sampling peripheral lesions is a viable alternative to reusable bronchoscopes for advanced bronchoscopy procedures.

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07-7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19-7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

Vitamin D in Systemic Sclerosis: A Review.

(1) Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc); (2) Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies. (3) Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent; (4) Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis.

Keep on tailoring CMV management in lung transplantation: 24 versus 12-month CMV hyperimmune globulins regimen effects in combined universal prophylaxis.

BACKGROUND: In lung transplantation (LTx), Cytomegalovirus (CMV) management is based on prophylaxis or pre-emptive therapy. CMV hyperimmune globulins (CMV IG) added to prophylactic antiviral agents reduce CMV manifestations and acute rejection. The length of prophylaxis regimens is variable among studies with different results. METHODS: We conduced, after demonstrating efficacy of 12 months prophylaxis on acute rejections and CMV pneumonia, a single center retrospective study comparing, during the second year after LTx, clinical effects of a long (24 months) versus short (12 months) course of combined CMV prophylaxis scheme, based on antiviral agents and CMV IG. RESULTS: We included 120 patients, 70 received a long (24 months) and 50 a short (12 months) prophylaxis. The long prophylaxis group, at 18th month, had a lower rate of neutrophilic alveolitis in BAL (63.6% vs. 94.4%, P=0.029). No other statistically significant differences were observed among the two groups of patients although we observed a reduction in both CMV (56.4% vs. 76.0% P=n.s.) and bacterial infections (23.7% vs. 32.0%, P=n.s.) during the 18th month of follow-up. We did not observe differences among two groups in acute rejection rate on transbronchial lung biopsies. CONCLUSIONS: The combined long prophylaxis course based on antiviral agents and CMV IG provides a reduction trend in CMV or bacterial infections even if not statistically significant. The significant reduction in neutrophilia in BAL compared to the cohort undergoing prophylaxis for 12 months should be carefully interpreted. An 18-month prophylaxis could be a good suggestion to be tested by other larger prospective studies.