Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment.

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

Prognostic importance of central thrombus in hemodynamically stable patients with pulmonary embolism.

BACKGROUND: The association between mortality and localization of central thrombus in hemodynamically stable patients with pulmonary embolism (PE) is unclear. Sufficient data are not available to help clinicians to select between low molecular weight heparin (LMWH), unfractionated heparin (UFH) and thrombolytics for the management of central thrombus. The present study aims to investigate whether central thrombus in the pulmonary artery affects 30-day mortality rate, and to compare the outcomes of different treatment approaches in patients with central thrombus. METHODS: This multi-central, prospective, observational study included 874 hemodynamically stable patients with PE confirmed by multidetector computed tomography scan. The localization of the emboli was evaluated and categorized as central (saddle or at least one main pulmonary artery), lobar or distal. The primary study outcome was 30-day all-cause mortality. RESULTS: Localization of the emboli was central in 319 (36.5%) patients, lobar in 264 (30.2%) and distal in 291 (33.2%) patients. Seventy-four (8.5%) patients died during the 30-day follow-up period. All-cause mortality rate was 11.9%, 6.8% and 6.2% in patients with central, lobar, and distal emboli, respectively (p < 0.001). Multivariate analysis did not show that hemodynamically stable central thrombus was an independent predictor of mortality. Additionally, mortality rate was not significantly different between UFH, LMWH and thrombolytic therapy groups. CONCLUSIONS: The present study showed that central thrombus was not an independent predictor of mortality in hemodynamically stable PE patients. LMWH and UFH were similarly effective in the treatment of this patient group.

Copeptin: a new predictor for severe obstructive sleep apnea.

INTRODUCTION: Copeptin which is the C-terminal fragment of antidiuretic hormone (ADH), is a biomarker that has been reported to be increased in various cardiovascular disorders, cerebrovascular diseases and associated with prognosis. Patients with obstructive sleep apnea syndrome (OSAS) have a tendency to develop coronary and cerebral atherosclerotic diseases. OBJECTIVES: The aim of the present study was to study copeptin levels in patients with obstructive sleep apnea and in a control group in order to determine whether copeptin could be used as a biomarker predicting the severity of OSAS and possible complications in this group. METHODS: A total of 116 patients with OSAS, diagnosed by polysomnography, and 27 controls were included in the study. Blood samples were collected after overnight fasting, and copeptin levels were measured with enzyme-linked immunosorbent assay. RESULTS: Copeptin levels were significantly higher in the OSAS group compared to control group (2,156±502; 1,845±500 pg/mL, respectively, P=0.004). Mean copeptin level of the patients having apnea-hypopnea index (AHI) ≥30 was significantly higher than that of the patients having AHI <30 (2,392±415; 2,017±500 pg/mL, respectively, P<0.001). A multivariate regression analysis showed that copeptin level, (hazard ratio: 1.58; 95% confidence interval: 1.09-2.30) was a predictor of severe OSAS (P=0.016). Copeptin levels showed significant positive correlation with AHI (r=0.32; P<0.001), desaturation index (r=0.23; P=0.012), arousal index (r=0.24; P=0.010) and CRP (r=0.26; P=0.011) respectively. CONCLUSION: Copeptin levels are high in OSAS patients and copeptin is a potential marker for identifying patients with a high risk of early cardiovascular complications of OSAS. Copeptin has modest sensitivity (84%) for discriminating severe OSAS patients who are candidates for severe cardiovascular complications.

The prognostic values of GDF-15 in comparison with NT-proBNP in patients with normotensive acute pulmonary embolism.

BACKGROUND: An early prediction of prognosis in pulmonary embolism (PE) is a crucial clinical entity. The aim of the study is to investigate whether growth differentiation factor-15 (GDF-15) or N-terminal pro-brain natriuretic peptide levels (NT-proBNP) can better predict the 30 day overall mortality in patients with normotensive acute PE. METHODS: Patients with a high clinical probability of PE, or with low/intermediate probability and a positive D-dimer test, underwent contrast-enhanced computed tomography and ventilation/perfusion lung scan. Simplified pulmonary embolism severity index, the presence of echocardiographic right ventricular dysfunction, and ROC curve analysis by calculated cut-off value of serum GDF-15 and NT-proBNP levels were evaluated for each individual of study population. RESULTS: The serum levels of GDF-15 and NT-proBNP were found to be significantly higher in patients with PE compared with controls (p < 0.0001). In this study, GDF-15 provided better results compared to NT-proBNP in predicting the short-term or 30 day mortality (p = 0.046 and p = 0.418, respectively). Serum GDF-15 with a cut-off value of > 2943 pg/mL yielded a 75% sensitivity, 68.7% specificity, 91.6% negative predictive value, and 90% accuracy for predicting 30 day overall mortality. The results of these tests were found as 62.5%, 40.6%, 81.2%, and 40% for NT-proBNP (with the cut-off value of > 1409 pg/mL), respectively. CONCLUSIONS: High serum GDF-15 levels may provide better information than NT-proBNP for early death in the subjects with normotensive PE and these patients should be closely followed up.

Cerebral fat embolism syndrome after long bone fracture due to gunshot injury.

Cerebral fat embolism syndrome is a lethal complication of long-bone fractures and clinically manifasted with respiratory distress, altered mental status, and petechial rash. We presented a 20-year-old male admitted with gun-shot wounds to his left leg. Twenty-four hours after the event, he had generalized tonic clonic seizures, decorticate posture and a Glascow Coma Scale of seven with localization of painful stimuli. Subsequent magnetic resonance imaging of the brain showed a star-field pattern defining multiple lesions of restricted diffusion. On a 4-week follow-up, he had returned to normal neurological function. Despite the severity of the neurological condition upon initial presentation, the case cerebral fat embolism illustrates that, cerebral dysfunction associated with cerebral fat embolism illustrates reversible.

Arterial stiffness measured via carotid femoral pulse wave velocity is associated with disease severity in COPD.

BACKGROUND: Patients with COPD face an increased risk of cardiovascular disease and increased cardiac mortality. Carotid femoral pulse wave velocity (cf-PWV) is a validated measure of arterial stiffness, a well recognized predictor of adverse cardiovascular outcomes, and offers higher predictive value than classical cardiovascular risk factors. We investigated the association between COPD and arterial stiffness using cf-PWV as a noninvasive technique. METHODS: This clinical study was prospective, observational, and cross-sectional. Sixty-two subjects with stable COPD and 22 healthy controls underwent physical examination, chest x-rays, pulmonary function tests, arterial blood gas analysis, and 6-min walk test, and cf-PWV was measured via a validated tonometry system. RESULTS: The COPD subjects had greater arterial stiffness than the control subjects, and that difference was associated with lower FEV1, PaO2, and oxygen saturation during the 6-min walk test. We observed higher cf-PWV in the COPD subjects with severe COPD than in the subjects with mild to moderate COPD. Only FEV1 was an independent predictor of cf-PWV. CONCLUSIONS: Our results suggest that arterial stiffness is increased in subjects with more severe and advanced COPD than in those with mild to moderate COPD. Air flow limitation and hypoxemia may induce increased arterial stiffness in COPD patients.

[Elevated pleural copeptin levels can distinguish to exudate from transudates]. / Yüksek plevral copeptin düzeyleri eksüdayi transüdadan ayirabilir.

INTRODUCTION: Copeptin is released simultaneously along with arginine-vasopressine as a result of different stimuli from the neurohypophysis. Physiological function of copeptin is still unclear. Increased blood copeptin levels is associated with poor prognosis in many diseases. Pleural effusion is a common clinical condition. The most common causes of pleural effusions are heart failure, parapneumonic effusion, pulmonary embolism and malignacy.Tuberculosis is one of the other major causes of pleural effusion in developing countries. In this study, we aimed to assess whether pleural copeptin level may be a new discriminative biomarker for exudates and transudates pleural effusions. MATERIALS AND METHODS: Research was done at Recep Tayyip Erdogan University School of Medicine in the Department of Chest Diseases. The concentrations of pleural copeptin and typical pleural and serum marker levels were measured in 76 subjects with pleural effusions including 22 transudates caused by congestive heart failure (CHF), and 54 exudates including 18 parapneumonic (PPE), 18 tuberculous pleural effusions (TBPEs), 18 malignant effusions (MPEs). RESULTS: Median pleural fluid copeptin levels were higher in exudates than in transudates (1936 ng/mL and 1313 pg/mL, p value < 0.001). There was no statistical significancy for pleural fluid copeptin levels with in-group exudates (n= 54). Pleural copeptin levels of exudates, with a cut off value of 1469 ng/mL, yielded a 79.6% sensitivity, 81.8% specificity, with an are a under the curve of 0.851. CONCLUSION: Pleural copeptin level is a new biomarker to separate exudates from transudates. Pleural effusion discriminative effect of copeptin is lower than plasma protein level and plasma lactat dehydrogenase (LDH). Pleural copeptin measurement is not recommended for routine clinical use. Pleural copeptin level is not contribute to different iate exudative pleural fluids from each other like PPE, TBPE and MPE.

The clinical utility of pleural YKL-40 levels in diagnosing pleural effusions.

BACKGROUND AND OBJECTIVE: Recent evidence suggests that YKL-40 is a relatively new biomarker of inflammation and it is involved in the pathogenesis of several pulmonary diseases. Details of serum and pleural YKL-40 in pleural effusions however, remain unknown. We aimed to assess whether serum and pleural YKL-40 is an accurate biomarker of pleural effusions. METHODS: This clinical study was prospective, observational and cross-sectional. The concentrations of serum and pleural fluid YKL-40 and conventional pleural marker levels were measured in 80 subjects with pleural effusions, including 23 transudates caused by congestive heart failure (CHF), and 57 exudates including 23 parapneumonic, 22 malignant and 12 tuberculous pleural effusions (TBPEs). RESULTS: Median pleural fluid YKL-40 levels were higher in exudates than in transudates (219.4 and 205.9 ng/mL, respectively, P<0.001). High pleural YKL-40 levels, with a cutoff value of >215 ng/mL, yielded a 73% sensitivity, 73% specificity, likelihood ratio 2.8 for diagnosing exudate, with an area under the curve of 0.770 [95% confidence intervals (CI): 0.657-0.884]. Pleural YKL-40/serum YKL-40 ratio >1.5 yielded a 75% sensitivity, 72% specificity and likelihood ratio 2.6 for diagnosing TBPE, with an area under the curve of 0.825 (95% CI: 0.710-0.940). CONCLUSIONS: High concentrations of pleural YKL-40 level may help to differentiate exudate from transudate and a high pleural YKL-40/serum YKL-40 ratio may be helpful in seperating TBPE from non-tuberculous effusions.

Effects of leflunomide on inflamation and fibrosis in bleomycine induced pulmonary fibrosis in wistar albino rats.

PURPOSES: Pulmonary fibrosis is a rare and progressive lung disease with a high mortality rate. The treatment regimens still fail to recover the disease. Leflunomide (LEF) is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. The purpose of the study is to investigate the potential therapeutic efficacy of LEF in bleomycin (BLM) induced pulmonary fibrosis. METHODS: A total of 21 male, adult wistar albino rats were used. The animals were divided into three groups as control, BLM and BLM plus LEF groups (n=7). In BLM group, mice were treated with intratracheal instillation of BLM (2.5 U/kg). Control group received the same volume of saline instead of BLM. In LEF group, in addition to BLM, LEF (10 mg/kg, daily) was administrated by oral gavage. The effect of LEF on pulmonary inflammation and fibrosis was studied by measurements of serum clara cell protein-16 (CC-16), thiobarbituric acid reactive substance levels (TBARS), superoxide dismutase (SOD) and advanced oxidation protein products (AOPP) levels and lung tissue contents of IL-6, TNF-α and NF-κB by immunhistochemical examinations. RESULTS: LEF significantly increased the level of CC-16 and decreased the level of AOPP (P=0.042 and P=0.003 respectively). Lung tissue contents of IL-6, TNF-α and NF-κB significantly decreased in LEF group compared to BLM group by immunhistochemical examinations (P<0.001). CONCLUSIONS: LEF reduces oxidative stress factors, alveolar inflammation and attenuates lung injury and fibrosis.

Prevalence of occupational asthma and respiratory symptoms in foundry workers.

This cross-sectional study was conducted in a foundry factory to assess the prevalence of respiratory symptoms and occupational asthma in foundry workers. Physical examination, spirometric evaluation, chest radiograph, and a questionnaire related to respiratory symptoms were performed. Monitoring of peak expiratory flow rates, spirometric reversibility test, and high-resolution computed tomographies were performed for the participants having respiratory symptoms and/or impaired respiratory function test. A total of 347 participants including 286 workers from production department and 61 subjects who worked in nonproduction departments were enrolled in this study. It is found that phlegm (n: 71, 20.46%) and cough (n: 52, 14.98%) were the most frequent symptoms. The other symptoms were breathlessness (n: 28, 8.06%), chest tightness (n: 14, 4.03%), and wheezing (n: 7, 2.01%) . The prevalence of occupational asthma was found to be more frequent among the subjects who worked in the production department (n: 48, 16.78% ) than the other persons who worked in the nonproduction department (n: 3, 4.91%) by chi-square test (P: 0.001). To prevent hazardous respiratory effects of the foundry production, an early diagnosis of occupational asthma is very important. Cessation of cigarette smoking and using of protective masks during the working time should be encouraged.

An unusual radiological presentation of a pulmonary hydatid cyst in a child.

Giant pulmonary hydatid cyst is usually encountered in adolescents and children who are older than 10 years. A relatively higher elasticity of the lung tissue allows rapid growth of cysts. We present a case of a 15-year-old male who was admitted with complaint of frequent and persistent dry cough for over a month. Computed tomographic scan revealed a giant cyst with thick enhancing rim and an "air bubble" sign. Diagnosis of giant hydatid cyst was confirmed by surgery and histopathological examination.

High serum YKL-40 level in patients with COPD is related to hypoxemia and disease severity.

Chronic obstructive pulmonary disease (COPD) is a major health problem with increasing morbidity and mortality throughout the world. YKL-40 is a chitin-binding glycoprotein consisting of 383 amino acids, with a molecular mass of 40 kDa, and its serum level is elevated in inflammatory diseases. YKL-40 is a newly recognized biomarker of inflammation and has not been thoroughly investigated in COPD. The aim of the study is to investigate the relationship between serum YKL-40 levels and severity of COPD. The study population consisted of 52 patients with COPD with the mean age of 60.2 ± 10.1 years. The serum YKL-40 level increased significantly with increasing age (p = 0.022, r = 0.346). In COPD patients, high serum YKL-40 level is correlated to low forced expiratory volume at 1 second (FEV1, percent of predicted) (r = -0.277, p = 0.047). Moreover, high serum YKL-40 level is correlated to low arterial oxygen pressure (PaO2, mmHg) (r = -0.387, p = 0.005). The mean serum YKL-40 level was found as 243.1 ± 129.2 ng/ml in COPD patients with desaturation during 6-minute walk test (6MWT) and this value was higher than the mean serum YKL-40 level (155.8 ± 59.1 ng/ml) of COPD patients without desaturation during 6MWT (p = 0.004). This study demonstrated that high serum YKL-40 levels were correlated to severity of COPD. We propose that circulating YKL-40 levels could be a biomarker for hypoxemia and decline in lung function.

Plasma viscosity levels in pulmonary thromboembolism.

Genetic and acquired thrombophilic risk factors may play role on developing venous thromboembolism (VTE). In many cases of pulmonary thromboembolism (PE) it can not be defined any explicit risk factor. In this study we aimed to identify the role of plasma viscosity level on PE. The investigation was planned prospectively and 33 patients with PE and 36 apparently healthy and nonsmoker volunteers as control group were enrolled in the study. The mean plasma viscosity levels were determined in patients with PE and in healthy volunteers as 1.42±0.30 cP and 1.29±0.22 cP respectively. The mean plasma viscosity levels was found to be different between PE and healthy group (p=0.009). The mean levels of triglyceride, fibrinogen and hematocrit were found different between patients with PE and control group (p<0.05). Variables including sex, age, smoking habits, levels of hematocrit, fibrinogen, total cholesterol and triglyceride were not associated with plasma viscosity values in patients with PE. Plasma viscosity levels were found higher in patients with PE compared with healthy indivudials. But it is needed to further studies to define the interactions between factors effecting blood rheology and development of thrombosis.

Intralobar pulmonary sequestration as an unusual cause of recurrent hemoptysis.

Pulmonary sequestration is an embryonic, cystic lung tissue that is supplied by systemic blood circulation. It is a nonfunctional lung parenchyma unconnected to normal tracheobronchial system. In cases of pulmonary sequestration, surgical interventions should be performed in order to prevent possible complications such as massive hemoptysis and infections. Preoperative imaging and treatment planning should be done carefully. We present an uncommon case of recurrent hemoptysis caused by intralobar pulmonary sequestration located in the left lower lobe.

[Histopathologically diagnosed pulmonary complicated hydatid cyst cases]. / Histopatolojik olarak tani konulan komplike akciger kist hidatik olgulari.

OBJECTIVE: Hydatid cyst disease is caused by the metacestod form of Echinococcosis granulosus from cestods. Pulmonary hydatid cyst is the second most frequent form of the disease after the liver involvement and may open into the bronchial or pleural space by perforation and may cause complications. The aim of the study was to evaluate the clinical features and the frequency of the complicated pulmonary hydatid cyst disease. METHODS: Fifteen hydatid cyst patients were evaluated according to socio-demographical, clinical and radiological findings between 2009 and 2011 retrospectively. Hydatid cyst diseases were diagnosed histopathologically after chest surgery. Diagnostic difficulties and clinical features were analysed in four complicated pulmonary hydatid cyst cases. RESULTS: Pneumothorax, pleural effusion, lung abscess, and hemoptysis were observed in four complicated cases. The complicated cases were diagnosed after surgery. Eleven of lung cysts were intact, radiological and histopathological features were typical for images of hydatid cyst disease and reported as compatible with the clinical diagnosis. A synchronized liver and pulmonary hydatid cyst was evaluated as a morbidity factor. CONCLUSION: Hydatid cyst should be considered in the differential diagnosis of uncertain chest pathologies, especially in rural areas where the disease is endemic.

Prevalence of asthma and respiratory symptoms by age, gender and smoking behaviour in Samsun, North Anatolia Turkey.

Asthma is a major health problem worldwide. This is the first study determining the prevalence of asthma among adults in Samsun which is situated in the centre of the Black Sea region of Turkey. The aim of our study was to assess the prevalence of asthma and asthmatic symptoms, and the relationships of these with age, gender and smoking behaviour in this region. A questionnaire interview adapted from the European Respiratory Community Health Survey (ERCHS) was performed by health centre officers with selected people between November-December, 2002. The study population included a total of 1.916 [810 men (42.3%) and 1.106 women (57.7%)] inhabitants of Samsun city center, aged 15 years of age or above. The mean age was 37.8 years+/-15.5, the prevalence of asthma was 2.7%, receiving asthma medicine was 2.2%, the prevalence of wheezing in the last 12 months was 15.5% and shortness of breath with wheezing was 11.6%. The frequency of symptoms was higher among the elderly population when compared to other groups (p<0.0001). Asthma diagnosis by a physician was more frequent among women (chi2=5.16, p<0.05). Morning cough, day time cough, chronic cough, phlegmy cough and waking up with cough symptoms were more frequent among the smokers (p<0.001). Asthma diagnosis and asthma treatment are at a very low level compared to reported asthma related symptoms.