Transbronchial lung cryobiopsy under real-time radial EBUS: First report on a novel twist of the classical technique.

Transbronchial lung cryobiopsy (TBLC) is a relatively new technique for obtaining lung biopsies, known for being the least invasive method while offering a high diagnostic yield, a favourable safety profile, and a significant reduction in morbidity, mortality, and hospital stay length compared to surgical lung biopsy. Radial-EBUS (r-EBUS) represent a cornerstone modality for accessing 'invisible' peripheral pulmonary lesions. However, a major drawback of these techniques is the lack of 'real-time' visualization of the biopsy being obtained. In this case report, we present a young woman who was referred to us with a cough, haemoptysis, and a non-resolving lung consolidation. She underwent TBLC under real-time rEBUS guidance. This clinical case demonstrates that, in specific clinical scenarios, TBLC with real-time rEBUS is an excellent diagnostic tool.

Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial).

INTRODUCTION: Despite many technological advances, the diagnostic yield of bronchoscopic peripheral lung nodule analysis remains limited due to frequent mispositioning. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic feedback on needle positioning, potentially improving the sampling location and diagnostic yield. Previous studies have defined and validated nCLE criteria for malignancy, airway and lung parenchyma. Larger studies demonstrating the effect of nCLE on diagnostic yield are lacking. We aim to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared with conventional bronchoscopy without nCLE. METHODS AND ANALYSIS: This is a parallel-group randomised controlled trial. Recruitment is performed at pulmonology outpatient clinics in universities and general hospitals in six different European countries and one hospital in the USA. Consecutive patients with a for malignancy suspected peripheral lung nodule (10-30 mm) with an indication for diagnostic bronchoscopy will be screened, and 208 patients will be included. Web-based randomisation (1:1) between the two procedures will be performed. The primary outcome is diagnostic yield. Secondary outcomes include diagnostic sensitivity for malignancy, needle repositionings, procedure and fluoroscopy duration, and complications. Pathologists will be blinded to procedure type; patients and endoscopists will not. ETHICS AND DISSEMINATION: Primary approval by the Ethics Committee of the Amsterdam University Medical Center. Dissemination involves publication in a peer-reviewed journal. SUPPORT: Financial and material support from Mauna Kea Technologies. TRIAL REGISTRATION NUMBER: NCT06079970.

Cone Beam Computed Tomography improves location of transbronchial cryobiopsy in interstitial lung disease with limited extent.

INTRODUCTION: transbronchial lung cryobiopsy has been recommended as an acceptable alternative to surgical approach for making a histopathological diagnosis in patients with Interstitial Lung Disease (ILD) of undetermined type. In limited diseases (especially if distributed along the sub-pleural region), sampling the specific area in which the pathological process is more represented could be challenging. Aim of the study was to determine the potential benefit of utilizing Cone Beam Computed Tomography (CBCT) guided cryobiopsy in patients with limited extent of ILD on CT scan and determine the single impact of each sequential biopsy progressively increasing the total number of biopsies. METHODS: prospective analysis of patients with undetermined ILD and CT scan extent < 15 % undergoing cone beam CT - guided cryobiopsy. Each biopsy sample was collected and processed individually and pathologic interpretations were performed sequentially with the pathologist reformulating a new report with the addition of each sample (cumulative yield). RESULTS: 36 patients were enrolled. Pathological diagnostic yield was very good (> 90%), with almost 80% of diagnostic samples being the first one; when a second biopsy was performed, mean diagnostic yield increased with only a moderately significant difference. No severe adverse events were observed, pneumothorax was documented in 27.8 % of the cases. CONCLUSION: sequential individual collection and pathologic interpretation of each biopsy sample has confirmed the possibility of obtaining a diagnostic specimen at the first pass if transbronchial cryobiopsy is performed under cone-beam CT.

Endobronchial ultrasound-guided cryobiopsy for diagnosing a case of granulomatosis with polyangiitis.

EBUS-TBNA has represented a revolution in the diagnosis of intrathoracic pathologies, particularly in lung cancer staging, replacing more invasive methods such as mediastinoscopy. However, its role in diagnosing rare benign or malignant mediastinal disorders is still a matter of debate. Over the past few years, the role of EBUS-guided cryobiopsy has been increasingly emerging as an innovative and minimally invasive technique in diagnosing these disorders, with an excellent safety profile. In this case report, we present the case of a young man brought to our attention after already undergoing a non-diagnostic trans thoracic needle aspiration (TTNA) procedure for lung consolidations. In our department, he underwent an initial EBUS-TBNA procedure with inconclusive rapid on-site evaluation (ROSE), leading to the decision to perform an EBUS-guided cryobiopsy, which yielded a diagnosis of granulomatosis with polyangiitis without complications. This clinical case demonstrates that in specific contexts, EBUS-cryobiopsy represents an excellent diagnostic tool.

Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

COVID-19. Biology, pathophysiology, and immunology: a pathologist view.

Even if the SARS-CoV-2 pandemic has been declared over, several risks and clinical problems remain to be faced, including long-COVID sequelae and possible outbreaks of pathogenic variants. Intense research on COVID-19 has provided in these few years a striking amount of data covering different fields and disciplines, which can help to provide a knowledge shield against new potential infective spreads, and may also potentially be applied to other fields of medicine, including oncology and neurology. Nevertheless, areas of uncertainty still remain regarding the pathogenic mechanisms that subtend the multifaceted manifestations of the disease. To better clarify the pathogenesis of the disease, a systematic multidisciplinary evaluation of the many mechanisms involved in COVID-19 is mandatory, including clinical, physiological, radiological, immunological and pathological studies. In COVID-19 syndrome the pathological studies have been mainly performed on autopsy cases, and only a few studies are available on biopsies. Nevertheless, these studies have provided relevant information that can substantially contribute to decipher the complex scenario characterizing the different forms of COVID-19 and long-COVID-19. In this review the data provided by pathological investigations are recapitulated and discussed, in the light of different hypothesis and data provided by clinical, physiological and immunological data.

Images in Sarcoidosis: new section of our Journal.

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A complicated case of whole-lung lavage: a case report.

Introduction: We report a life-threatening case of severe respiratory failure due to a pulmonary alveolar proteinosis (PAP) secondary to lysinuric protein intolerance (LPI), complicated by a pre-existing right pneumothorax, which we treated using a rescue whole-lung lavage (WLL). To date, in the literature, there are no cases of WLL performed in this condition. Clinical condition: Patient was referred to our center because of rapidly worsening dyspnea and deterioration of gas exchange, caused by a secondary form of PAP which required an immediate therapeutic option such as the one offered by WLL. On physical examination, bilateral crackles were present, and peripheral blood oxygen saturation was 78% on oxygen with a FiO2 of 40%. Interventions: After stabilizing the clinical conditions with oxygen therapy erogated through a high-flow nasal cannula, shortly after admission, we performed a rescue WLL among two procedures. The procedure was very effective, and the patient was later discharged without oxygen therapy and in good clinical condition. Conclusion: Our case report represents a chance to help fill the gap of knowledge relative to secondary forms of PAP. The patient we presented suffers from a very rare genetic condition (LPI) that only has a few reported cases in the literature and has a very low prevalence which makes it difficult to produce the affected people:newborns ratio. We believe that difficult and rare cases like this one can improve our understanding of the disease and, most importantly, of how much the only therapeutic option we had, a rescue WLL, is effective to improve gas exchange and radiological features, despite being performed in these severe respiratory conditions.

Historical eye on IPF: a cohort study redefining the mortality scenario.

Rationale: Therapies that slow idiopathic pulmonary fibrosis (IPF) progression are now available and recent studies suggest that the use of antifibrotic therapy may reduce IPF mortality. Objectives: The aim of the study was to evaluate whether, to what extent, and for which factors the survival of IPF in a real-life setting has changed in the last 15 years. Methods: Historical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral center for ILDs with prospective intention. We recruited all consecutive IPF patients seen at GB Morgagni Hospital, Forlì, Italy between January 2002 and December 2016 (15 years). We used survival analysis methods to describe and model the time to death or lung transplant and Cox regression to model prevalent and incident patient characteristics (time-dependent Cox models were fitted). Measurements and main results: The study comprised 634 patients. The year 2012 identifies the time point of mortality shift (HR 0.58, CI 0.46-0.63, p < 0.001). In the more recent cohort, more patients had better preserved lung function, underwent cryobiopsy instead of surgery, and were treated with antifibrotics. Highly significant negative prognostic factors were lung cancer (HR 4.46, 95% CI 3.3-6, p < 0.001), hospitalizations (HR 8.37, 95% CI 6.5-10.7, p < 0.001), and acute exacerbations (HR 8.37, 95% CI 6.52-10.7, p < 0.001). The average antifibrotic treatment effect estimated using propensity score matching showed a significant effect in the reduction of all-cause mortality (ATE coeff -0.23, SE 0.04, p < 0.001), acute exacerbations (ATE coeff -0.15, SE 0.04, p < 0.001), and hospitalizations (ATE coeff -0.15, SE 0.04, p < 0.001) but no effect on lung cancer risk (ATE coeff -0.03, SE 0.03, p = 0.4). Conclusion: Antifibrotic drugs significantly impact hospitalizations, acute exacerbations, and IPF survival. After the introduction of cryobiopsy and antifibrotic drugs, the prognosis of IPF patients has significantly improved together with our ability to detect IPF at an earlier stage.

Clinical implications of interstitial pneumonia with autoimmune features diagnostic criteria in idiopathic pulmonary fibrosis: A case control study.

Background: A subgroup of IPF patients can meet IPAF criteria (features suggesting an underlying autoimmune process without fulfilling established criteria for a CTD). This study was aimed to evaluate whether IPAF/IPF patients compared to IPF patients differ in clinical profile, prognosis and disease course. Methods: This is a retrospective, single center, case-control study. We evaluated 360 consecutive IPF patients (Forlì Hospital, between 1/1/2002 and 28/12/2016) and compared characteristics and outcome of IPAF/IPF to IPF. Results: Twenty-two (6%) patients met IPAF criteria. IPAF/IPF patients compared to IPF were more frequently females (N = 9/22, 40.9% vs. N = 68/338, 20.1%, p = 0.02), suffered more frequently from gastroesophageal reflux (54.5% vs. 28.4%, p = 0.01), and showed a higher prevalence of arthralgias (86.4% vs. 4.8%, p < 0.0001), myalgias (14.3% vs. 0.3%, p = 0.001) and fever (18.2% vs. 1.9%, p = 0.002). The serologic domain was detected in all cases (the most frequent were ANA in 17 and RF in nine cases) and morphologic domain (histology features) was positive in 6 out of 10 lung biopsies (lymphoid aggregates). Only patients with IPAF/IPF evolved to CTD at follow-up (10/22, 45.5%; six rheumatoid arthritis, one Sjögren's and three scleroderma). The presence of IPAF was a positive prognostic determinant (HR 0.22, 95% CI 0.08-0.61, p = 0.003), whereas the isolated presence of circulating autoantibody did not impact prognosis (HR 1.00, 95% CI 0.67-1.49, p = 0.99). Conclusion: The presence of IPAF criteria in IPF has a major clinical impact correlating with the risk of evolution to full blown-CTD during follow-up and identifying a subgroup of patients with a better prognosis.

Is there any role for medical thoracoscopy in the treatment of empyema in children?

It is still controversial whether surgical or nonsurgical treatment approaches are most appropriate for empyema in children, and there are no data regarding the role of medical thoracoscopy in this population. The aim of this study was to describe our experience with medical thoracosocpy in children with multiloculated and organizing pneumonia. We retrospectively reviewed children admitted to our hospital with a diagnosis of empyema from 2011 to 2021 and treated with medical thoracoscopy. A total of six patients with empyema were treated by medical thoracoscopy; empyema was multiloculated in five cases and organized in one case; all children in the study recovered completely with full lung expansion after chest X-rays, and no disease sequelae were reported after clinical follow-up. Our small case series suggests that in selected cases, medical thoracoscopy could safely and effectively treat pleural empyema in children, with less invasiveness and reduced psychological consequences.

Medical Thoracoscopy and Intrapleural Fibrinolytic Therapy for the Management of Pleural Empyema: A Cohort Study.

BACKGROUND: Pleural empyema is associated with relevant morbidity and mortality, and it may be classified, according to evolution and ultrasound, into three stages: stage I (free-flowing effusion), stage II (viscous effusion with the tendency to loculate), and stage III (organizing phase). According to guidelines, antibiotic therapy and pleural drainage are recommended, with surgery being performed when patients fail and/or in case of organized empyema. OBJECTIVES: The aim of the study was to report the efficacy and safety of medical thoracoscopy in patients with pleural empyema stratified by chest ultrasound. METHOD: Observational retrospective cohort study analyzing patients with pleural empyema treated with medical thoracoscopy. Procedure success and mortality were evaluated at 30 days and 90 days after the procedure; complications were also reported. RESULTS: 131 patients were included. Intrapleural fibrinolytic therapy was performed thereafter in the majority of cases. Medical thoracoscopy was considered successful without subsequent intervention in 99 patients (76%); 19 patients (15%) underwent a second procedure (drainage, thoracoscopy, video-assisted thoracic surgery, or thoracotomy); and 6 patients (5%) died of the evolution of empyema. Patients treated in stages I and II showed significantly better post-procedure results compared with patients treated in stage III (100%, 83.3%, and 58.1%, respectively). Thoracoscopy complications were observed in 18 patients and were reversible in all cases. CONCLUSIONS: Patients with pleural empyema treated in earlier stages (free-flowing or multiloculated effusion) with medical thoracoscopy show significantly better results than patients treated in later stages (organized empyema). This approach is safe, minimally invasive, and efficient in these patients with disease having relevant mortality; however, patient selection remains essential.

Lung cancer in patients with idiopathic pulmonary fibrosis: A retrospective multicentre study in Europe.

BACKGROUND AND OBJECTIVE: There remains a paucity of large databases for patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. We aimed to create a European registry. METHODS: This was a multicentre, retrospective study across seven European countries between 1 January 2010 and 18 May 2021. RESULTS: We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence = 10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer (HR: 1.51, [95% CI: 1.22-1.86], p < 0.0001). All-cause mortality was significantly lower for patients with IPF and lung cancer with a monocyte count of either <0.60 or 0.60-<0.95 K/µl than patients with monocyte count ≥0.95 K/µl (HR [<0.60 vs. ≥0.95 K/µl]: 0.35, [95% CI: 0.17-0.72], HR [0.60-<0.95 vs. ≥0.95 K/µl]: 0.42, [95% CI: 0.21-0.82], p = 0.003). Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics (HR: 0.61, [95% CI: 0.42-0.87], p = 0.006). In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients (HR: 0.30 [95% CI: 0.11-0.86], p = 0.02). CONCLUSION: Lung cancer exerts a dramatic impact on patients with IPF. A consensus statement for the management of patients with IPF and lung cancer is sorely needed.