The Fagerström Test for Nicotine Dependence, as a prognostic factor, in current smokers with and without COPD: A cross-sectional study in northern Greece.

BACKGROUND: Smoking poses the most common risk factor for chronic obstructive pulmonary disease (COPD) and aggravates disease progression. Tobacco dependence inhibits smoking cessation and may affect smoking patterns that increase tobacco exposure and predispose to lung function decline. AIMS AND OBJECTIVES: We aimed to assess tobacco dependence in current smokers with and without COPD and evaluate its role in disease development. METHOD: This cross-sectional study was conducted in Greek rural areas. Current smokers completed the Fagerström Test for Nicotine Dependence and were classified into COPD and non-COPD groups based on spirometry parameters. RESULTS: Among current smokers, 288 participants comprised the non-COPD and 71 the COPD group. Both presented moderate tobacco dependence, but smokers with COPD started to smoke earlier in the morning. Multiple logistic regression analysis revealed higher COPD prevalence in smokers with higher scores in the Fagerström test (odds ratio OR = 1.12, 95% confidence interval [1.01 - 1.24]) and older age (OR = 1.06 [1.03 - 1.09]), independently of pack-years smoking index. Multiple linear regression analysis in smokers with COPD showed that the forced expiratory volume in the 1st second decreased by 2.3% of the predicted value for each point increase in the Fagerström Test and 0.59% for each year of age, independently of participants' sex and pack-years smoking index. CONCLUSION: The Fagerström score appears to indicate a higher probability for COPD and lung function deterioration when assessed along with age in current smokers. Smoking cessation support programs are fundamental to COPD prevention and management.

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

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.

Celiac disease and idiopathic pulmonary hemosiderosis: a literature review of the Lane-Hamilton syndrome.

Lane-Hamilton syndrome (LHS) presents a medical emergency, with 14% mortality due to Idiopathic Pulmonary Hemosiderosis (IPH) in acute phase. Despite the clinical severity of this entity, there has been no published review in the international literature, resulting in lack of awareness and delayed diagnosis.A rigorous search of international databases yielded a total of 80 LHS cases from January 1971 to August 2020. We analyzed 44 children (8.56 ± 4.72 years, 21 boys) and 36 adults (33.61 ± 13.41 years, 12 men) to present the clinical manifestations, radiological and immunological pattern, therapeutic approaches and outcome of LHS. We also elaborated on clinical and laboratory findings' associations to propose diagnostic indexes and clarified differences based on age distribution.Celiac disease (CD) and IPH diagnosis was made concurrently in 46 patients, whereas in 21 patients, the diagnosis of LHS was delayed for 2.5y (3 months-11 years). Hemoptysis (n = 56, 70%), dyspnea (n = 47, 58.8%), anemia (n = 72, 90%), and iron deficiency (n = 54, 67.5%) were most commonly observed. Medical history revealed recurrent episodes of hemoptysis (n = 38) and persistent iron deficiency anemia (n = 25) in need of multiple blood transfusions or iron supplementation. Patchy infiltrate opacities to consolidation predominated in children, whereas bilateral diffuse ground-glass opacities in adults. Duodenal biopsy was performed in 66 cases (diagnostic 87.8%), BAL in 51 (diagnostic 74.5%), and surgical lung biopsy in 20. Anti-tTG titer was positive in all 24 (54.6%) children and 19 (52.8%) adults that documented this assay. Prednisone or methylprednisolone pulse therapy and GFD were initiated in the acute phase, whereas chronic therapy included GFD, along with long-term prednisone in refractory cases. Three cases with severe respiratory failure or hemodynamic instability were intubated and a further three succumbed.A thorough understanding of LHS may reveal further diagnostic indexes and a consensus on therapy guidelines. Screening for CD is essential in all IPH cases for timely recognition and favorable outcome.

Mesothelioma: A Case in a Diagnostic Timeline and the Efficiency of Robot-Assisted Surgery.

We present a case of a 65-year-old male with a difficulty to diagnose mesothelioma. To be specific, three attempts were made to diagnose the disease, and only with a large sample performed with robot-assisted surgery, our pathologists were able to identify the malignancy. The novelty for our case is mostly based on the timeline of the diagnosis along with the tissue samples where we present the course of the transformation from benign to malignancy. All tissue biopsies were checked by two independent pathologists. Conclusively, diagnosis for small local lesions should be performed with an endoscopic method, video-assisted or robot-assisted.

Radial Endobronchial Ultrasound for Lung Cancer Diagnosis: Tips and Tricks.

Introduction: Endoscopic techniques have been upgraded in the recent 10 years. We can use the radial endobronchial ultrasound to reach distal nodules in the periphery of the lungs, but also we can use it in order to make biopsies in lesions without endobronchial findings. Patients and Methods: We included in our study 248 patients with pulmonary nodules up to 4 cm. We use a radial endobronchial system from FUJI, a PENTAX bronchoscope and a C-ARM. We recorded the cancer type, biopsy method, time of each procedure, cell blocks and slices from cell blocks. Results: Two thirds of patients belonged to males (61.7%), forceps was the main tissue extraction technique (118, 47.6%) and tumors sized 1 to 2 cm were the most encountered (96, 38.7%). Samples with tissue content were present in 175 patients (70.6%) and one cell block dominated in the samples (109, 43.9%). Less than 20 minutes were needed to complete the operative procedure for the half patients (127, 51.2%), the C-Arm implementation concerned 117 persons (47.2%) and the majority of tumors was located in the central area of the lungs (178, 71.8%). Less time was necessary for central lesions and larger biopsy samples were acquired without the extensive use of C-ARM. Conclusion: The larger the nodule ≥2cm and in periphery the less we use the C-ARM and the time of the procedure is between 20-40 minutes. Moreover; we have more tissue sample and cell block slices.

Perinatal management of enlarged bronchogenic cyst causing hydrops fetalis.

Bronchogenic cysts are rare congenital anomalies that they are usually diagnosed prenatally during the routine second trimester scan. We present such a rare case of bronchogenic cyst in a fetus. Our initial scan demonstrated a big cystic mass, which enlarged progressively causing shifting of the mediastinum and compression of the fetal heart. Consequent hydrops fetalis was treated with thoracoamniotic shunt and the pregnancy continued with no further complications. Pontnatal period, surgery and long term follow-up was uneventful.

Tracheal fistula repair with stent placement after failure of reconstruction with muscle tissue. A lung cancer surgery complication.

A report a case of a 63 year old male diagnosed with lung cancer adenocarcinoma. The patient had a right paratracheal mass diagnosed with EBUS-TBNA 22G. The patient had surgery, however 7 days after the billau catheter was removed pneumothorax was diagnosed which did not resolved. Bronchoscopy reveled two minor fistulas in the interior wall of the trachea. An additional surgery was performed in order to add muscle patches on the exterior part of the trachea. Unfortunately additional stent placement was placed after a silicon stent since the muscle patches failed. We chose a metallic auto expandable stent since after three months of follow up a small metastatic lesion was observed in the liver. Stent placement is an option for these patients and the right stent has to be placed for each case.

Lymphadenopathy and granulomas: benignancy of malignancy and differential diagnosis with endobronchial ultrasound-transbronchial needle biopsy 19G needle fine-needle aspiration biopsy.

Endobronchial ultrasound (EBUS) is a very useful tool for the diagnosis of lymphadenopathy of the mediastinum. Nowadays, EBUS can substitute video-assisted thoracic surgery when a 19G needle is used. Several studies have provided data for efficient diagnosis not only for lung cancer, but for also sarcoidosis, tuberculosis and lymphoma. We present five cases of EBUS-transbronchial needle biopsy 19G needle used for the diagnosis of mediastinum lymphadenopathy. We present not only the pathological diagnosis, but also the steps for the differential clinical and pathological differential diagnosis for sarcoidosis, tuberculosis, cancer metastasis, respiratory infection and lymphoma.

Interventional bronchoscopy for HPV 16 and 66 with the use of spraying interferon-α (2b) plus bevacizumab and anti-reflux agent.

A fifty year old male was diagnosed with bronchial HPV. He was treated with local interventional treatment argon plasma coagulation and subcutaneous injections bevacizumab. Spraying of the regions followed with a specially designed catheter with interferon-α (2b). Systematic treatment of esomeprazole was also administered. After six months the patient is disease free and on close follow-up.

Bronchogenic cyst or lung cancer. Only biopsy can tell.

Bronchogenic cysts are rare congenital malformations which derive from primitive ventral foregut. They are usually observed in intrathoracically. A fifty year old male was admitted for the investigation of a three month chest pain. Computed tomography scan of the thorax revealed a lesion around the esophagus and left stem bronchus. Endobronchial ultrasound with convex probe and a 19G needle biopsy revealed a bronchogenic cystic which was removed with video assisted thoracic surgery. Initial radiologic assessment although was thought to be lung cancer because of the smoking habit it turned out to be benignancy. EBUS-TBNAB with 10G needle is safe and absolutely necessary for these lesions, as they take large samples.

Vapor for lung volume reduction; pros and cons.

INTRODUCTION: Bronchoscopic lung volume reduction (BLVR) is a novel approach for treatment of emphysema. Several techniques are available to accomplish BLVR including Bronchoscopic Vapor Thermal Ablation (BVTA). This technique is easy to perform and considered safe due to its gradual effect. We discuss BTVA in detail in this editorial. AREAS COVERED: We discuss our experience with BTVA in detail including patient selection, equipment, procedure, post-procedural care and complications. We also review the literature to determine the pros and cons for its use. Other modalities such as endobronchial valves, coils and lung sealants are also briefly discussed. EXPERT OPINION: Vapor ablation is a novel and safe approach in inducing lung volume reduction in emphysema patients. The effects are gradual, and therefore potentially making it safer than other minimally invasive modalities. Pneumonitis and infection are common side effects. Just as in other BLVR techniques, a case by case evaluation is needed to determine the right candidate for BTVA. Further larger studies are needed before BTVA becomes standard of care in treatment of patients with emphysema.

Bronchial HPV; the good the bad and the unknown.

BACKGROUND: Solitary tracheobronchial papilloma (STBP) is a rare benign tumor. Human papilloma virus (HPV) infection is associated with dysplasia and a high risk of carcinoma. CASE 1: Sixty five year old male with hemoptysis and with coilocytic atypia, indicating the presence of HPV. CASE 2: Thirty two year old female with a polypoid villoglandular bronchial structure and no cytoplasmic or nuclear atypia but prominent microvilli. DISCUSSION: Tissue sample is the best sample in order to determine and distinguish the two entities, local treatment should be considered as first option when possible.

Sex Differences and Adverse Effects between Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer.

Introduction: Lung cancer remains the leading cause of cancer mortality in men and women and around the world. Approximately 90% of cases of lung cancer are caused by smoking and the use of tobacco products. However, other factors such as asbestos, air pollution and chronic infections can contribute to pulmonary carcinogenesis. Lung cancer is divided into two broad histological categories, which develop and spread different small cell lung carcinomas and non-small cell lung carcinomas. The treatment options for lung cancer include surgery, radiotherapy, chemotherapy and targeted treatments. Tumor induced immune suppression is vital for malignant progression. Immunotherapies act by strengthening the patient's innate tendency for an immune response and give positive promise to patients with non-small cell lung cancer and small cell lung cancer. Immune checkpoint inhibitors are a new approach to cancer therapies. Just as immune therapies include a new approach to cancer biology, the toxicities associated with these factors have created new challenges in clinical practice. Materials & Methods: Patients (218) aged 40-80 years were treated with either chemotherapy or immunotherapy. Their response to treatment and any subsequent adverse drug reactions were studied. Results: 69% of patients were treated with chemotherapy and 31% were treated with immunotherapy. The type of treatment had a statistically significant effect on the undesirable effects of the treatment. Conclusions: The type of treatment was statistically significant in responding to the treatment and treatment side effects but not in the rate of death.

Extended resections for the treatment of patients with T4 stage IIIA non-small cell lung cancer (NSCLC) (T4N0-1M0) with or without cardiopulmonary bypass: a 15-year two-center experience.

BACKGROUND: Stage IIIA non-small cell lung cancer (NSCLC) is a heterogeneous group of patients, often requiring variable and individualized approaches. The dilemma to operate or not frequently arises, since more than 75% of the cases of NSCLC are diagnosed in advanced stages (IIIA). The main objective of this study was to assess whether the benefits outweigh surgical risks for the T4N0-1M0 subgroup. METHODS: Data from 857 patients with locally advanced T4 NSCLC were retrospectively collected from two different institutions, between 2002 and 2017. Clinical data that were retrieved and analyzed, included demographics, comorbidities, surgical details, neoadjuvant or/and adjuvant therapy and postoperative complications. RESULTS: Twelve patients were in the cardiopulmonary bypass (CPB) group and thirty in the non-CPB. The most common types of lung cancer were squamous cell carcinoma (50.0%) and adenocarcinoma (35.7%). The most frequent invasion of the tumor was seen in main pulmonary artery and the superior vena cava. Significantly more patients of the CPB group underwent pneumonectomy as their primary lung resection (P=0.006). In all patients R0 resection was achieved according to histological reports. The overall 5-year survival was 60%, while the median overall survival was 22.5 months. Analysis revealed that patient age (P=0.027), preoperative chronic obstructive pulmonary disease (COPD) (P=0.001), tumor size (4.0 vs. 6.0 cm) (P=0.001), postoperative respiratory dysfunction (P=0.001) and postoperative atelectasis (P=0.036) are possible independent variables that are significantly correlated with patient outcome. CONCLUSIONS: We suggest that in patients with stage IIIA/T4 NSCLC, complete resection of the T4 tumor, although challenging, can be performed in highly selected patients. Such an approach seems to result in improved long-term survival. More specific studies on this area of NSCLC probably will further enlighten this field, and may result in even better outcomes, as advanced systemic perioperative approaches such as modern chemotherapy, immunotherapy and improvements in radiation therapy have been incorporated in daily practice.

Ex situ reimplantation technique, in central lung tumors.

BACKGROUND: The parenchyma-sparing resection is most often performed in patients with impaired preoperative lung or cardiovascular function who would not be able to tolerate a pneumonectomy. METHODS: Our experience on the ex situ reimplantation procedure and the outcome of patients with lung malignancies, who underwent upper or upper-middle lobectomy, with reimplantation of the lower lobe was reported. RESULTS: We present 9 patients mean age 62.6+16.2 years (7 males/2 females) underwent ex situ reimplantation due to extensive lung tumor of upper lobes. The surgical technique precludes IV heparinization and then radical pneumonectomy. The entire lung was immersed in Ringer's solution (temperature 4 degrees centigrade) and bench surgery was performed. The involved upper (or upper-middle) lobes with involved lymph nodes were resected, thus leaving the healthy lower lobe of the lung. Pneumoplegia solution, named "Papworth pneumoplegia", was administered (1,473 mL) through catheterization of the pulmonary artery and vein stumps (ante grade and retrograde) along with 250 mL of prostaglandin E1. Re-implantation of the lower lobe was performed (I) on the right side, implantation involved the anastomosis of lower pulmonary vein in the site of the cuff of left atrium, followed by suturing the stump of the intermedius pulmonary artery to the right main pulmonary artery and finally the bronchial stumps-intermedius bronchus to the right main bronchus; (II) on the left side the pulmonary vein was anastomosed first, followed by the bronchial stumps and finally by the pulmonary artery. The graft ischemia time was 70.2+8.4 minutes ranged between 55 and 80 minutes. CONCLUSIONS: Re-implantation or auto-transplantation should be considered as a safe option for the appropriate patient with lung cancer. The ex situ separation of the cancerous lobes is technically feasible and allows extensive pulmonary resection while minimizing the loss of pulmonary reserve. Based on our work, the major factors that play a role for the survival of initially resected and then re-implanted lung graft, are: (I) the ischemia time of the re-implanted lobe; (II) the proper use of pneumoplegia solutions, along with prostaglandin E1 and heparin; (III) the occurrence of pulmonary vein thrombosis; and (IV) the bronchial anastomosis.

Operation for preservation of lung parenchyma in central lung cancer--in vivo and ex situ reimplantation techniques.

BACKGROUND/AIM: Lobar reimplantation techniques enable the safe resection of lung cancer when pneumonectomy is not desirable or not feasible. We report our experience with this procedure. PATIENTS AND METHODS: Patients with difficult to resect upper/middle lobe non-small cell lung cancer were included. In situ reimplantation technique requires the reanastomosis of the pulmonary vein of the healthy lower lobe to the upper lobe stump; bench surgery reimplantation involves the ex vivo surgical treatment of the whole excised lung and subsequent reimplantation of the healthy remnant. RESULTS: Nine patients with upper-middle lobe lung cancer underwent in situ reimplantation, mean age=70.7±4.2 years; 6 patients underwent ex situ resection, mean age=64.3±18.4 years. One obese patient succumbed due to thrombosis of the anastomosed pulmonary vein. One patient developed a stroke. CONCLUSION: The procedure was in general well-tolerated and enables for curative resection of otherwise unresectable lung cancer.

Excessive muscle paralysis due to pulmonary carcinoid -a case report.

We present the case of a 58-year-old woman with a renin secreting typical bronchopulmonary carcinoid. This patient showed hypotension, constipation and fatigue due to extensive hypokaliemia (K =1.9 meq/L). Aldosterone (102.7 ng/100 mL) and renin (46 ng/mL) were excessively elevated at that time, but cortisol level was normal. Routine chest roentgenography and computed tomography revealed a nodular lesion in the upper left lung lobe, which was suspicious for a neurosecretory pulmonary tumor. The final diagnosis was made by using bronchoscopic procedures and the histologically diagnosis was compatible as a typical pulmonary carcinoid. The tumor was resected curatively, and the renin and aldosterone level became normal. A year after the patient looks healthy.

Solitary papillomas of the lower airways: epidemiological, clinical, and therapeutic data during a 22-year period and review of the literature.

INTRODUCTION: Solitary respiratory papillomas (SRPs) are considered uncommon yet benign neoplasms of the lower respiratory tract. Most of our understanding stems from single case reports or limited case series. OBJECTIVE: To determine the incidence of solitary SRPs and more accurately describe the localization, distribution of subtypes of solitary SRPs, clinical features, and the risk of malignant transformation. This retrospective report is based on data collected in a busy single-center bronchoscopy practice during a 22-year period. METHODS: Among 36,780 patients who underwent bronchoscopic procedures between 1986 and 2008, we identified 32 patients with SRPs. This patient group was compared with 69 patients with SRPs described in the English literature as case reports, case series, or diagnostic dilemmas. RESULTS: Twenty-three patients were men (male/female ratio of 3:1), and 21 patients were former smokers (65.6%). The mean age of initial presentation in men and women was 56.9 ± 14.3 versus 53.3 ± 14.4 years, respectively. The presenting symptoms included cough in 18 patients (40.6%), hemoptysis in 11 (25%), dyspnea in seven (21.8%), and fever in five patients (15.7%). Two patients with papillomas in the subglottic region had wheezing and were on aerosolized bronchodilator therapy. In one patient, the papilloma was incidentally discovered on a chest computed tomography scan. The histologic analysis of lesions revealed squamous papillomas in 65.6%, a glandular subtype in 18.75%, and a mixed subtype in 15.6%. Malignant transformation was observed in five patients (15.7%). The malignancies consisted of squamous cell carcinoma in two patients, and single cases of small cell lung carcinoma, glandular carcinoma, and low-grade carcinoma. CONCLUSION: In our experience, the estimated incidence of SRPs is 3.95 cases/100,000 patients/yr. SRPs occur more commonly in men (ratio 3:1). Squamous papillomas occur commonly during the fifth decade of life, glandular papillomas predominate in the sixth decade, and the distribution of mixed type papillomas is from the third to the sixth decade of life. Malignant transformation was observed in a minority of patients.