Use of Next-Generation Sequencing to Support the Diagnosis of Familial Interstitial Pneumonia.

Familial interstitial pneumonia (FIP) is defined as idiopathic interstitial lung disease (ILD) in two or more relatives. Genetic studies on familial ILD discovered variants in several genes or associations with genetic polymorphisms. The aim of this study was to describe the clinical features of patients with suspected FIP and to analyze the genetic variants detected through next-generation sequencing (NGS) genetic testing. A retrospective analysis was conducted in patients followed in an ILD outpatient clinic who had ILD and a family history of ILD in at least one first- or second-degree relative and who underwent NGS between 2017 and 2021. Only patients with at least one genetic variant were included. Genetic testing was performed on 20 patients; of these, 13 patients had a variant in at least one gene with a known association with familial ILD. Variants in genes implicated in telomere and surfactant homeostasis and MUC5B variants were detected. Most variants were classified with uncertain clinical significance. Probable usual interstitial pneumonia radiological and histological patterns were the most frequently identified. The most prevalent phenotype was idiopathic pulmonary fibrosis. Pulmonologists should be aware of familial forms of ILD and genetic diagnosis.

Secondary Organising Pneumonia Among COVID-19 Patients: A Retrospective Case-Control Study.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Secondary organising pneumonia (OP) induced by SARS-CoV-2 infection is a recently recognised complication of COVID-19. We aimed to evaluate the prevalence of OP among hospitalised patients with COVID-19 pneumonia and to assess whether disease severity and other clinical factors and comorbidities are correlated with OP development. We conducted a retrospective case-control study including hospitalised patients due to COVID-19 who performed a chest CT scan during hospitalisation and compared patients with clinical and radiological evidence of OP to patients without evidence of OP. Demographics, comorbidities, disease severity, dexamethasone/remdesivir treatment, laboratory results, and outcomes were compared between groups. One hundred fifteen patients were included, of whom 48 (41.7%) fulfilled clinical and imaging criteria for OP. Among OP patients, the most common chest CT-scan findings were consolidations, arciform condensations, and subpleural bands. OP patients had longer hospitalisation (19.5 vs 10 days, p=0.002) and more frequent ICU admission, but no significant differences in readmittance or mortality rates within 180 days compared to controls. In the adjusted effects model, the need for supplementary oxygen on the 21st day after symptom onset, the presence of Ordinal Scale for Clinical Improvement (OSCI) = 4, when compared to OSCI ≤ 3, and higher C-reactive protein on admission, were significantly associated with higher odds for OP. No other differences were identified between OP and controls after adjusting for other factors. The use of remdesivir or dexamethasone did not impact the diagnosis of OP. Only 38% of OP patients required treatment with high-dose corticosteroids. In conclusion, SARS-CoV-2-induced OP may be more frequent than previously thought, especially among hospitalised patients and patients with a more severe disease, particularly those who fail to improve after the second week of disease or who present higher inflammatory markers on admission. It increases the length of stay, but not all patients require specific treatment and OP may improve despite the absence of high-dose corticosteroid treatment.

Peripheral blood eosinophilia may be a prognostic biomarker in non-small cell lung cancer patients treated with immunotherapy.

BACKGROUND: Eosinophils have been traditionally associated with the initiation and propagation of inflammatory responses, particularly in allergic diseases and helminth infections. More recently, an association between eosinophils and cancer has been the focus of several studies, but controversial results have emerged. This study aims to evaluate the prognostic role of peripheral blood eosinophilia in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We also evaluated the impact of peripheral eosinophilia on the occurrence of immune-related adverse effects (irAEs). METHODS: Advanced NSCLC patients under IO were included in a retrospective single-center study. Peripheral blood eosinophilia was defined by a count greater than 500/µL. Patients were analyzed for eosinophil counts, overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). RESULTS: A total of 121 NSCLC patients receiving IO were included. Thirty-three (27.3%) patients presented peripheral blood eosinophilia during treatment. Patients with peripheral eosinophilia presented more frequently non-progression as best overall response to IO (83.3% vs. 58.1%, P=0.014), higher median OS (26.6 vs. 9.5 months, P=0.022) and higher median PFS (13.8 vs. 4.6 months, P=0.013). IrAEs were more common in patients with peripheral eosinophilia (66.7% vs. 36.4%, P=0.003). CONCLUSIONS: This study suggests that peripheral blood eosinophilia may predict better outcomes in NSCLC patients receiving IO, despite being associated with an increased risk of irAEs. According to our findings eosinophils may be involved in immune response against tumor. Routine eosinophils count assessment may be an additional prognostic tool in NSCLC patients receiving IO.

Conventional versus pigtail chest tube-are they similar for treatment of malignant pleural effusions?

INTRODUCTION: The optimal chest tube type and size for drainage and chemical pleurodesis of malignant pleural effusions remains controversial. This retrospective study was conducted to compare the efficacy of conventional versus pigtail chest tube in the treatment of malignant pleural effusions. METHODS: Patients submitted to chest tube drainage and slurry talc pleurodesis due to malignant pleural effusion in our pulmonology ward from 2012 to 2016 were eligible. According to the type of chest tube, they were divided into two groups: group I-conventional chest tube and group II-pigtail chest tube. Number of deaths, recurrence of malignant pleural effusion, and timelines associated with the procedures were reviewed and compared between groups. RESULTS: Out of the 61 included patients, 46 (75.4%) were included in group I and 15 (24.6%) in group II. Only one patient had pigtail chest tube obstruction, with posterior insertion of conventional chest tube. Death during hospital stay and up to 3 months, recurrence at 4 weeks, total duration of hospital stay, time from chest tube insertion to pleurodesis, and time from chest tube insertion to removal were not significantly different between the two groups (all p > 0.05). DISCUSSION: These findings suggest that pigtail chest tube can be an alternative on palliation, with no compromise in pleurodesis performance.

Lung cancer in never-smokers - what are the differences?

INTRODUCTION: Characteristics of never-smokers with lung cancer are still not fully clarified. The aim of this study was to compare never-smokers and ever-smokers with non-small cell lung cancer (NSCLC) regarding patient and tumor characteristics. METHODS: All consecutive newly NSCLC patients with known smoking status diagnosed between 2011 and 2015 were included in this retrospective cohort study. Clinical, histological, and molecular characteristics were compared between ever-smokers and never-smokers. RESULTS: Of the 558 included patients, 125 (22.4%) were never-smokers. These patients were more likely to be female (74% vs. 7%, p < .001), older (67 vs. 66 years-old, p = .019), and have adenocarcinoma (93% vs. 65%, p < .001). Never-smokers took longer to seek medical care after the symptoms onset (3 vs. 2 months, p < .001), regardless of the symptoms, histological type, or gender (OR: 1.2 [1.4-2.0]). The metastatic pattern was different in never-smokers: pleural metastases were more frequent (OR: 2.1 [1.1-4.0]), regardless of the histological type and gender. Never-smokers had a higher prevalence of ALK translocations (26% vs. 4%, p < .001) and EGFR mutations (36% vs. 8%, p < .001). The type of EGFR mutation was also significantly different between groups. CONCLUSIONS: Never-smokers with NSCLC present distinct demographic and clinical characteristics. The characteristics of tumor also differ between never-smokers and ever-smokers, which may suggest different carcinogenic pathways.

Prognostic impact of M descriptors of the 8th edition of TNM classification of lung cancer.

BACKGROUND: The 8th edition of the tumor, node and metastasis (TNM) classification of lung cancer will be enacted in January 2017. The aim of this study was to analyze the survival differences among the three new categories of metastatic disease: intrathoracic metastasis (M1a), single extrathoracic metastasis (M1b) and multiple extrathoracic metastases (M1c) in our cohort of patients with non-small cell lung cancer (NSCLC). METHODS: This is a retrospective single-center study including NSCLC patients with metastatic disease at diagnosis. Patients were divided into three groups (M1a, M1b, M1c). Overall survival (OS) within and between these subgroups was calculated using the Kaplan-Meier method. RESULTS: A total of 288 patients were included (112 M1a, 28 M1b and 148 M1c). Median OS of M1c was significantly worse than M1a or M1b tumors (P<0.001). No significant differences were found among the M1a descriptors (pleural/pericardial nodules/effusion, bilateral tumor nodules or both descriptors) (P=0.722) and between M1a and M1b tumors (P=0.517). OS of patients with one metastasis in a single organ was not significantly different from OS of patients with two metastases in a single organ (P=0.180). Among M1c tumors, OS was significantly better in patients with multiple metastases in a single organ than in patients with multiple metastases in multiple organs (P=0.001). CONCLUSIONS: Our results support the proposal to keep the M1a category unchanged in the 8th edition as well as the proposed restructuring of the M1b in the new M1b and M1c categories. However, our results raise questions about the definition of oligometastatic disease and, consequently, the criteria of M1b and M1c category.

Isolated tuberculous lymphadenitis with tracheal involvement in an elderly patient.

Mediastinal tuberculosis without lung involvement is an uncommon finding in an immunocompetent adult. We report the case of an 80-year-old male smoker who presented with dyspnea and stridor. He was found to have a mass in the middle mediastinum which also involved the anterior wall and 50% lumen if of the lower trachea. Histology and mycobacterial cultures of the lesion led to the diagnosis of mediastinal tuberculosis. Antituberculous treatment led to complete resolution of airway symptoms and reduction in the size of the mediastinal mass.