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.

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.

Molecular Mechanism in the Development of Pulmonary Fibrosis in Patients with Sarcoidosis.

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called advanced pulmonary sarcoidosis, APS) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetic factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic characteristics and molecular pathways which are believed to be associated with the development of APS.

Predictors of pulmonary sequelae after COVID-19 pneumonia: A 12-month follow-up study.

Background: Since the beginning of the SARS-CoV-2 pandemic, over 550 million people have been infected worldwide. Despite these large numbers, the long-term pulmonary consequences of COVID-19 remain unclear. Aims: The aim of this single-center observational cohort study was to identify and characterize pulmonary sequelae of COVID-19 at 12 months from hospitalization and to reveal possible predictors for the persistence of long-term lung consequences. Methods: Based on the persistence or absence of radiological changes after 12 months from hospitalization, the whole population was categorized into NOT-RECOVERED (NOT-REC) and RECOVERED (REC) groups, respectively. Clinical and pulmonary function data tests and clinical data were also collected and compared in the two groups. In the NOT-REC group, high resolution computed tomography (HRCT) images were semiquantitatively scored analyzing ground-glass opacities (GGO), interstitial thickening (IT), consolidations (CO), linear and curvilinear band opacities, and bronchiectasis for each lung lobe. Logistic regression analyses served to detect the factors associated with 12-month radiological consequences. Results: Out of the 421 patients followed after hospitalization for SARS-CoV-2 pneumonia, 347 met inclusion and exclusion criteria and were enrolled in the study. The NOT-REC patients (n = 24; 6.9%) were significantly older [67 (62-76) years vs. 63 (53-71) years; p = 0.02], more frequently current smokers [4 (17%) vs. 12 (4%); p = 0.02], and with more severe respiratory failure at the time of hospitalization [PaO2/FiO2 at admission: 201 (101-314) vs. 295 (223-343); p = 0.01] compared to REC group (n = 323; 93.1%). On multivariable analysis, being a current smoker resulted in an independent predictor for lung sequelae after 12 months from hospitalization [5.6 OR; 95% CI (1.41-22.12); p = 0.01]. Conclusion: After 12 months from hospital admission, a limited number of patients displayed persistent pulmonary sequelae with minimal extension. Being a current smoker at the time of SARS-CoV-2 infection is an independent predictive factor to lung consequences, regardless of the disease severity.

The role of immune response in the pathogenesis of idiopathic pulmonary fibrosis: far beyond the Th1/Th2 imbalance.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unknown origin characterized by progressive scarring of the lung leading to irreversible loss of function. Despite the availability of two drugs that are able to slow down disease progression, IPF remains a deadly disease. The pathogenesis of IPF is poorly understood, but a dysregulated wound healing response following recurrent alveolar epithelial injury is thought to be crucial. AREAS COVERED: In the last few years, the role of the immune system in IPF pathobiology has been reconsidered; indeed, recent data suggest that a dysfunctional immune system may promote and unfavorable interplay with pro-fibrotic pathways thus acting as a cofactor in disease development and progression. In this article, we review and critically discuss the role of T cells in the pathogenesis and progression of IPF in the attempt to highlight ways in which further research in this area may enable the development of targeted immunomodulatory therapies for this dreadful disease. EXPERT OPINION: A better understanding of T cell interactions has the potential to facilitate the development of immune modulators targeting multiple T cell-mediated pathways, thus halting disease initiation and progression.

The clinical relevance of lymphocyte to monocyte ratio in patients with Idiopathic Pulmonary Fibrosis (IPF).

Disease course in Idiopathic Pulmonary Fibrosis (IPF) is highly heterogeneous and markers of disease progression would be helpful. Blood leukocyte count has been studied in cancer patients and a reduced lymphocyte to monocyte ratio (LMR) has been show to predict survival. Thus, we aimed to investigate the role of monocytes count and LMR in three distinct population of patients with IPF: 77 newly-diagnosed IPF, 40 with end-stage IPF and 17 IPF with lung cancer. In newly-diagnosed IPF patients, we observed a negative correlation between forced vital capacity (FVC) at diagnosis and both white blood cells and monocytes count (r = -0.24; p = 0.04 and r = -0.27; p = 0.01; respectively). Moreover, a high monocytes count was independently associated with functional decline (OR: 1.004, 95%CI 1.00-1.01; p = 0.03). In newly-diagnosed IPF, the LMR cut-off at diagnosis was 4.18 with an AUC of 0.67 (95%CI 0.5417-0.7960; p = 0.025), and overall survival was significantly worse in patients with a LMR<4.18 compared to patients with a LMR≥4.18 (HR: 6.88, 95%CI 2.55-18.5; p = 0.027). LMR was significantly lower in IPF patients with lung cancer compared to those newly diagnosed with IPF [2.2 (0.8-4.4), 3.5 (0.8-8.8); p < 0.0001] and those with end-stage disease [3.6 (2-6.5); p < 0.0001]. In conclusion, a LMR<4.18 is associated with significantly shorter survival in newly-diagnosed IPF patients. In addition, LMR is significantly lower in patients with IPF and lung cancer compared to patients with newly-diagnosed IPF. High monocytes count at baseline negatively correlates with FVC and is an independent predictor of disease progression in newly-diagnosed IPF patients.

Pulmonary Sarcoidosis: Diagnosis and Differential Diagnosis.

Sarcoidosis is a multisystem disorder of unknown origin and poorly understood pathogenesis that predominantly affects lungs and intrathoracic lymph nodes and is characterized by the presence of noncaseating granulomatous inflammation in involved organs. The disease is highly heterogeneous and can mimic a plethora of other disorders, making diagnosis a challenge even for experienced physicians. The evolution and severity of sarcoidosis are highly variable: many patients are asymptomatic and their disease course is generally benign with spontaneous resolution. However, up to one-third of patients develop chronic or progressive disease mainly due to pulmonary or cardiovascular complications that require long-term therapy. The diagnosis of sarcoidosis requires histopathological evidence of noncaseating granulomatous inflammation in one or more organs coupled with compatible clinical and radiological features and the exclusion of other causes of granulomatous inflammation; however, in the presence of typical disease manifestations such as Löfgren's syndrome, Heerfordt's syndrome, lupus pernio and asymptomatic bilateral and symmetrical hilar lymphadenopathy, the diagnosis can be established with high level of certainty on clinical grounds alone. This review critically examines the diagnostic approach to sarcoidosis and emphasizes the importance of a careful exclusion of alternative diagnoses.

Characteristics and Prognostic Factors of Pulmonary Fibrosis After COVID-19 Pneumonia.

BACKGROUND: Few is known about the long-term pulmonary sequelae after COVID-19 infection. Hence, the aim of this study is to characterize patients with persisting pulmonary sequelae at follow-up after hospitalization. We also aimed to explore clinical and radiological predictors of pulmonary fibrosis following COVID-19. METHODS: Two hundred and 20 consecutive patients were evaluated at 3-6 months after discharge with high-resolution computed tomography (HRCT) and categorized as recovered (REC) or not recovered (NOT-REC). Both HRCTs at hospitalization (HRCT0), when available, and HRCT1 during follow-up were analyzed semiquantitatively as follows: ground-glass opacities (alveolar score, AS), consolidations (CONS), and reticulations (interstitial score, IS). RESULTS: A total of 175/220 (80%) patients showed disease resolution at their initial radiological evaluation following discharge. NOT-REC patients (45/220; 20%) were mostly older men [66 (35-85) years vs. 56 (19-87); p = 0.03] with a longer in-hospital stay [16 (0-75) vs. 8 (1-52) days; p < 0.0001], and lower P/F at admission [233 (40-424) vs. 318 (33-543); p = 0.04]. Moreover, NOT-REC patients presented, at hospital admission, higher ALV [14 (0.0-62.0) vs. 4.4 (0.0-44.0); p = 0.0005], CONS [1.9 (0.0-26.0) vs. 0.4 (0.0-18.0); p = 0.0064], and IS [11.5 (0.0- 29.0) vs. 0.0 (0.0-22.0); p < 0.0001] compared to REC patients. On multivariate analysis, the presence of CONS and IS at HRCT0 was independent predictors of radiological sequelae at follow-up [OR 14.87 (95% CI: 1.25-175.8; p = 0.03) and 28.9 (95% CI: 2.17-386.6; p = 0.01, respectively)]. CONCLUSIONS: In our population, only twenty percent of patients showed persistent lung abnormalities at 6 months after hospitalization for COVID-19 pneumonia. These patients are predominantly older men with longer hospital stay. The presence of reticulations and consolidation on HRCT at hospital admission predicts the persistence of radiological abnormalities during follow-up.