George Kouliatsis

Serum biomarkers in interstitial lung diseases

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.

Prognostic factors in patients presenting with pleural effusion revealing malignancy.

Background: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. Methods: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. Results: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. Conclusion: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures.

Recombinant tissue plasminogen activator in the treatment of pleural infections in adults

BACKGROUND Intrapleural recombinant tissue plasminogen activator (r-TPA) has been successfully evaluated in pediatric patients with complicated parapneumonic pleural effusion (CPE) and pleural empyema (PE). Yet, there is no data concerning r-TPA in adults with CPE/PE. The aim of our study was to investigate the efficacy and complications of r-TPA in adult patients with CPE/PE. METHODS Twenty consecutive patients (mean age 50+/-18.9 years) with pleural infection (14 CPE and 6 PE) were included. Chest tube was inserted under guidance of chest ultrasound and/or computed tomography. After failure of pleural fluid drainage, 25mg of r-TPA was administered intrapleurally in a single daily dose. The evaluation was made according to imaging and clinical status. RESULTS The mean volume of fluid increased significantly after r-TPA administration (p<0.0001). White blood cells count (WBC) and C-reactive protein (CRP) were significantly improved after r-TPA instillations (both p<0.0001). Significant clinical and imaging improvement was noted in all but one patient after r-TPA administration (overall p<0.0001). Complications observed were mild: pain in 4 (25%) and local bleeding in 3 (15%) patients. The median number of r-TPA instillations was 3 (range 2-5). CONCLUSION Intrapleural instillation of r-TPA at a dose of 25 mg is a well-tolerated and effective treatment in 95% of our adult patients with CPE/PE.

Rare Cases of Primary Pleural Hodgkin and Non-Hodgkin Lymphomas

Primary pleural lymphoma is rare. It occurs in only 7% of lymphoma cases. We report herein two cases of primary pleural Hodgkin and non-Hodgkin follicular lymphomas diagnosed by thoracoscopy under local anesthesia. Both patients presented initially with dyspnea revealing pleural effusions. The pleural findings during thoracoscopy differed in the two cases and selective pleural biopsies under optical forceps led to the diagnosis of lymphoma. To date, primary pleural Hodgkin and non-Hodgkin follicular lymphomas have not been reported.

Respiratory Muscle Strength and Lung Function in Patients Undergoing Medical Thoracoscopy

Background: Medical thoracoscopy (MT) is a procedure considered as minimally invasive. The safety of the procedure has been questioned recently in fragile patients, but no explanation of the pathophysiologic mechanism has been given. Although MT is applied by respiratory physicians who are also dealing with patients with impairment of lung function, it is surprising that there are no data concerning lung mechanics and function in this patient population. Objectives: To assess respiratory muscle strength and lung function in patients undergoing MT, with or without talc pleurodesis. Methods: We measured prospectively the maximal inspiratory (MIP) and expiratory pressures (MEP) and lung function of 29 patients who underwent MT before (baseline) and on consecutive days following MT. Results: 29 patients participated with a mean age of 63.6 ± 13.8 (range 20–79) years. 15 of them underwent talc pleurodesis and 14 diagnostic thoracoscopy. Mean MIP and MEP values were significantly decreased on day (d) 1 after MT compared to baseline (p = 0.03 and p = 0.007, respectively) and recovered on d2. FEV1 and FVC mean values were also found significantly decreased on d1 after MT compared to baseline (p < 0.0001 and p = 0.0003, respectively) and recovered on d2. Patients with pleurodesis presented with lower mean values of the studied parameters than those with diagnostic thoracoscopy. No significant complication was associated with the procedure. Conclusion: Respiratory muscles and lung function can be temporarily affected from MT. Physicians should be alert, especially in patients with already impaired lung function, where any further impairment could be detrimental.

Long-term respiratory follow-up of H1N1 infection

BackgroundThe first case of 2009 pandemic influenza A (H1N1) virus infection was documented in our Hospital on 10th August 2009.Metdods and findingsReal-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm the diagnosis. All patients were treated with oseltamivir from the first day of hospitalization. Upon admission 12/44 had local patchy shadowing in their chest x-ray and additionally antibiotic regimen was added to these patients as pneumonia was suspected based on clinical evidence. In total 44 patients were hospitalized 15/44 had asthma, 6/44 COPD, 5/44 leukemia. Lung function was evaluated with forced vital capacity, forced expiratory volume in 1 sec and diffused carbon monoxide upon discharge and every 3 months, until 6 months of observation was completed after discharge. The purpose of this retrospective cohort study was to evaluate whether influenza A (H1N1) had an impact on the respiratory capacity of the infected patients.ConclusionsAn improvement of pulmonary function tests was observed between the first two measurements, implicating an inflammatory pathogenesis of influenza A (H1N1) to the respiratory tract. This inflammation was not associated with the severity or clinical outcome of the patients. All patients had a mild clinical course and their respiratory capacity was stable between the second and third measurement, suggesting that the duration of respiratory inflammation was two months. Early treatment with antiviral agents and vaccination represent the mainstay of management.

Intrapleural r-tPA in association with low-molecular heparin may cause massive hemothorax resulting in hypovolemia.

The use of intrapleural instillation of recombinant tissue plasminogen activator (r-tPA) in the treatment of pleural infection may increase pleural fluid drainage associated with a clinical and imaging improvement, leading to a faster resolution. The use of r-tPA is generally well tolerated. Here we report 2 cases of massive pleural hemorrhage resulting in life-threatening hypovolemia, in 2 patients treated with intrapleural r-tPA for a pleural infection, who were simultaneously receiving systemic anticoagulation (1 therapeutic, the second prophylactic) with low-molecular weight heparin. It appears that the decision of treating pleural infection with r-tPA in patients receiving therapeutic or prophylactic systemic anticoagulation must be well balanced and in case of association of these compounds, close monitoring is necessary.

Post-intubation pulmonary embolism and tracheal stenosis: A case report and review of the literature

Tracheal stenosis may be attributed to several conditions including trauma, infection, tumour or congenital and collagen vascular diseases. Despite improvement in the design of tracheal tubes, however, tracheal stenosis following intubation still remains an important cause for tracheal obstruction, which may be life threatening and often misdiagnosed. On the other hand, studies have exerted the impact of mechanical ventilation as a risk factor for pulmonary embolism. Here, we describe for the first time, an otherwise healthy patient who was mechanically ventilated due to a labor accident and developed acute pulmonary embolism that was further complicated with post-intubation tracheal stenosis. The patient was treated with anticoagulant therapy and oral corticosteroids and was further referred to a specialist centre for consideration for non-surgical endoscopic treatment.

Acute Respiratory Distress due to Thymoma in a Patient Treated with TK Inhibitor: A Case Report and Review of the Current Treatment Options

Thymic malignancies are rare intrathoracic tumors that may be aggressive and difficult to treat in advanced stage. Surgery is the cornerstone of the management of thymomas: it is significant for the definite histopathological diagnosis and staging, and in most cases, it constitutes the first step of the treatment strategy. For patients with primary unresectable thymomas, the multimodal treatment schedule nowadays includes neoadjuvant chemotherapy, extensive surgery, adjuvant radiotherapy, and in some cases, adjuvant chemotherapy. A patient with a history of stage III COPD and an undiagnosed thoracic mass was admitted to the intensive care unit with acute respiratory distress. A radiologic evaluation by CT scan revealed a mass of 13 cm in diameter at the mediastinum. Fine needle aspiration was performed and revealed a thymoma. Due to poor performance status, the patient was not able to undergo surgery. He refused to be treated with neither chemotherapy nor radiotherapy, but due to EGFR overexpression, treatment with TK inhibitor was suggested. Fine needle aspiration biopsy is commonly used to identify metastasis to the mediastinum. However, it is less often employed as a primary diagnostic tool for tumors, particularly thymic neoplasms. The use of targeted therapies for the treatment of thymic malignancies has been described in the literature. Over the past years, significant efforts have been made to dissect the molecular pathways involved in the carcinogenesis of these tumors. Insights have been obtained following anecdotal clinical responses to targeted therapies, and large-scale genomic analyses have been conducted.