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Endocrine paraneoplastic syndromes in lung cancer.

Paraneoplastic syndromes are defined as a combination of clinical disorders associated with malignant diseases that are caused by the secretion of various substances by the tumor without, however, being caused by the direct growth and infiltration of the primary tumor, or due to the development of distant metastases. Despite the fact that lung cancer represents the number one cause of death from cancer worldwide, the new methods of treatment increase patient survival and the incidence of paraneoplastic syndromes. The most important ones of these are humoral hypercalcemia of malignancy, syndrome of inappropriate antidiuretic hormone, hyponatremia of malignancy, ectopic Cushing's syndrome, carcinoid syndrome, and hypoglycemia and are usually a poor prognostic marker. Early diagnosis of those syndromes is achieved using specific criteria and may lead to early diagnosis of the underlying malignancy. It is essential to treat them with the overriding objective of improving the patients' quality of life.

Sleep disorders and health-related quality of life in patients with interstitial lung disease.

BACKGROUND: Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients' quality of life in relation to these disorders. METHODS: Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life, all patients completed the Short-Form 36 (SF-36) questionnaire. RESULTS: Of the IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2% with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate severity OSA. The remaining 42.8% did not have OSA. The health-related quality of life in both patients with IPF and patients with sarcoidosis was impaired especially in the domains concerning physical health and the level of independence, compared to the control group. CONCLUSIONS: In this sample of patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in a mild degree of severity. The SF-36 questionnaire may be a useful tool for the evaluation of the quality of life in these patients.

Techniques for assessing small airways function: Possible applications in asthma and COPD.

In recent years special interest has been expressed for the contribution of small airways in the pathophysiology, clinical manifestations and treatment of asthma and COPD. Small airways contribute little to the total respiratory resistance so that extensive damage of small airways may occur before the appearance of any symptoms, and this is the reason why they are characterized as the "silent zone" of airways. Furthermore, the peripheral localization of the small airways and their small diameter constitutes difficult their direct assessment. Thus, they are usually studied indirectly, taking advantage of the effects of their obstruction, such as premature closure, air trapping, heterogeneity of ventilation, and lung volume dependence of airflow limitation. Today, several heterogeneous methods for the assessment of small airways are available. These can be either functional (spirometry, plethysmography, resistance measurements, nitrogen washout, alveolar nitric oxide, frequency dependence of compliance, flow-volume curves breathing mixture of helium-oxygen) or imaging (mainly through high resolution computed tomography). The above-mentioned methods are summarized in Table 1. However, no method is currently considered as the "gold standard" and it seems that combinations of tests are needed. Furthermore, it is not clear whether the small airways are affected in all patients with asthma or COPD and their clinical significance remains under investigation. Well-designed future studies with large numbers of patients are expected to reveal which of the methods for assessing the small airways is the most accurate, reliable and reproducible, for which patients, and which can be used for the evaluation of the effects of treatment.

Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like cells in cryptogenic organizing pneumonia.

BACKGROUND AND OBJECTIVE: Natural killer (NK) cells appear to be involved in the development of interstitial lung diseases (ILD). The purpose of this study was to investigate the involvement of NK and natural killer T (NKT)-like cells in two recognized cytotoxic ILD with systemic character, hypersensitivity pneumonitis (HP) and cryptogenic organizing pneumonia (COP), compared with idiopathic pulmonary fibrosis (IPF) and controls. METHODS: Bronchoalveolar lavage fluid (BALF) and peripheral blood (PBL) cells and lymphocyte subsets of 83 patients (26 with COP, 19 with HP and 38 with IPF) and 10 controls were prospectively studied by flow cytometry. RESULTS: The percentage of NK and NKT-like cells was lower in BALF than in PBL in all patient groups and controls. Patients with COP presented with statistically significantly higher NK and NKT-like cell counts in BALF compared with controls (P = 0.044 and P = 0.05 respectively) and IPF (P = 0.049 and P = 0.045 respectively). BALF NKT-like cell count correlated with PBL NKT-like cell count only in COP (r = 0.627, P = 0.002). In addition, a significant positive correlation between BALF NKT-like cell and PBL cytotoxic T CD8+ cell count was observed in COP (r = 0.562, P = 0.006) but not in HP, IPF or controls. CONCLUSIONS: Our study provides for the first time evidence for the implication of NKT-like cells in the pathogenesis of COP, as part of both localized and systemic cytotoxicity.

Enteral nutrition intolerance in critically ill septic burn patients.

The purpose of this study was to investigate the frequency of enteral feeding intolerance in critically ill septic burn patients, the effect of enteral feeding intolerance on the efficacy of feeding, the correlation between the infection marker (procalcitonin [PCT]) and the nutrition status marker (prealbumin) and the impact of feeding intolerance on the outcome of septic burn patients. From January 2009 to December 2012 the data of all burn patients with the diagnosis of sepsis who were placed on enteral nutrition were analyzed. Septic patients were divided into two groups: group A, septic patients who developed feeding intolerance; group B, septic patients who did not develop feeding intolerance. Demographic and clinical characteristics of patients were analyzed and compared. The diagnosis of sepsis was applied to 29% of all patients. Of these patients 35% developed intolerance to enteral feeding throughout the septic period. A statistically significant increase in mean PCT level and a decrease in prealbumin level was observed during the sepsis period. Group A patients had statistically significant lower mean caloric intake, higher PCT:prealbumin ratio, higher pneumonia incidence, higher Sequential Organ Failure Assessment Maximum Score, a longer duration of mechanical ventilation, and a higher mortality rate in comparison with the septic patients without gastric feeding intolerance. The authors concluded that a high percentage of septic burn patients developed enteral feeding intolerance. Enteral feeding intolerance seems to have a negative impact on the patients' nutritional status, morbidity, and mortality.

Monitoring changes in quality of life in patients with lung cancer by using specialised questionnaires: implications for clinical practice.

BACKGROUND: Quality of life (QoL) in lung cancer patients is overlooked due to the severity of the disease. Changes in factors comprising QoL need further exploration to determine therapy targets. METHODS AND MATERIALS: QoL was assessed in 282 patients referred to a specialised centre in Greece for chemotherapy using three reliable scales: Functional Assessment of Cancer Therapy-Lung (FACT-L, Greek version 4), Short Form (SF-36) Health Survey and Hospital Anxiety and Depression Scale (HAD)S. RESULTS: Comparing QoL scores, it was observed that in comparison to the first chemotherapy, there was a statistically significant deterioration in patients' physical well-being (p < 0.0001) at the following chemotherapies. In contrast, there was a statistically significant improvement in patients' emotional well-being (p < 0.0001), mental health (p < 0.0001) and social functioning (p = 0.006) in the chemotherapies following the first. Observations deriving from survival analyses agree with literature findings: small cell lung cancer (SCLC) patients had significantly shorter survival than non-SLSC (NSCLC) patients, initial performance status was consistent with survival, radiotherapy improved survival, existence of metastases hindered survival, and the number of chemotherapies and QoL scores were positively correlated with survival. CONCLUSIONS: Although patients' physical functioning deteriorated after chemotherapy, their psychological state, mental health and social functioning improved in comparison with their first chemotherapy. This may be due to the fear of the unknown and the stress patients experience before their treatment. Regarding survival analysis results, it could be stated that the better QoL scores, the longer the survival. The findings underline the importance of psychological support after diagnosis and during the initiation of treatment. This may result in a better QoL, hence leading to prolongation of survival.

NK cell populations in collagen vascular disease.

OBJECTIVES: Pulmonary involvement of varying etiology is common in collagen vascular diseases (CVDs). Bronchoalveolar lavage fluid (BALF) cell differentials reveal information on the immune mechanisms involved in the CVDs. The aim of the present study was to evaluate BALF cell populations in CVD-associated ILD and to investigate possible correlation with pulmonary function. METHODS: Fifty-seven patients (26 male and 31 female, mean age ± SD: 54.68±12.18 years) with CVD-associated interstitial lung disease were studied. Patients were divided into 6 groups based on underlying CVD. The study population also included a group of 10 healthy controls. BALF was examined in all individuals. Cell density, total cell number and differential cell count were recorded. BALF lymphocyte subsets were analysed by dual flow cytometry. Pulmonary function was assessed in all patients. RESULTS: BALF differential cell count did not differ significantly among the different groups. Scleroderma patients showed the highest percentage of CD19 cells (p<0.001). The NK and NKT cell percentages were significantly higher in systemic lupus erythematosus and in Sjögren, respectively, compared to other CVDs and controls (p=0.001 and p<0.001). Also BALF neutrophil percentage correlated negatively with FVC (r=-0.356, p=0.011) and FEV1 (r=-0.336, p=0.017) and BALF NKT cell percentage correlated negatively with pO2 (r=-0.415, p=0.003). CONCLUSIONS: Important variations observed in BALF cell populations suggest the implication of NK and NKT cells in the pathogenesis of lung involvement in CVDs.

Spirometry values in a Greek population: is there an appropriate reference equation?

BACKGROUND AND OBJECTIVE: Most published reference values for lung function test (LFT) parameters introduce systematic bias. The aim of this study was to compare measured values of FEV(1) and FVC with the corresponding normal predicted values in a Greek population, and to produce reference equations for LFT parameters in this population. METHODS: In a cross-sectional study conducted in Macedonia, Greece, 1080 adult healthy, non-smokers (432 men, 648 women, aged 18-80 years), underwent spirometry. Measured values of FVC and FEV(1) were compared with predicted values determined using three existing sets of reference equations: one recently derived from a European population and two others widely used in Europe (European Coal and Steel Community; ECSC) and the USA (National Health and Nutrition Examination Survey; NHANES III). Height and age were entered into the multivariate regression analysis to produce reference equations for LFT parameters. RESULTS: All three published sets of equations underpredicted FEV(1) in men. FVC was accurately predicted by all equations except NHANES III. The discrepancy was even greater among women; the ECSC equation underpredicted both FEV(1) and FVC, the NHANES III equation overpredicted both FEV(1) and FVC, while the third set of equations accurately predicted FEV(1) but overpredicted FVC. The derived reference equation for FEV(1) in men was -0.28 × age + 0.057 × height - 4.91, and in women -0.021 × age + 0.039 × height - 2.58. The derived reference equation for FVC in men was -0.28 × age + 0.071 × height - 6.763, and in women -0.019 × age + 0.056 × height - 5.018. CONCLUSIONS: Measured FEV(1) and FVC values in a Greek population differed significantly from those predicted using previously published reference equations. The new locally derived spirometry reference equations may be more suitable for evaluation of lung function in everyday practice.

Total antioxidant status in patients with obstructive sleep apnea without comorbidities: the role of the severity of the disease.

OBJECTIVE: Several studies suggest that obstructive sleep apnea syndrome (OSAS) is associated with oxidative stress. However, there are also contrary observations and the role of antioxidant mechanisms has not been fully explored. PATIENTS AND METHODS: The present study evaluated serum total antioxidant status (TAS) in 32 OSAS patients without comorbidities, before and after a diagnostic sleep study and at a second sleep study after continuous positive airway pressure (CPAP) application. RESULTS: Lower TAS values were found in the morning, immediately after the first sleep study, compared with those before sleep (1.68 ± 0.11 vs. 1.61 ± 0.10 mmol/l, p < 0.01); this was evident in patients with less severe syndrome [apnea-hypopnea index (AHI) <30; 1.73 ± 0.08 vs. 1.65 ± 0.09 mmol/l, p = 0.01] but not in severe syndrome (AHI ≥30; 1.64 ± 0.12 vs. 1.58 ± 0.10 mmol/l, p = 0.07). After CPAP application, a statistically significant decrease in TAS values was observed in patients with less severe syndrome (1.72 ± 0.05 vs. 1.63 ± 0.04 mmol/l, p = 0.003). On the contrary, no statistically significant changes in TAS were observed in patients with severe syndrome. CONCLUSIONS: The present study supports a reduction in antioxidant capacity during sleep in otherwise healthy patients with OSAS. This reduction was evident in less severe syndrome. However, a single night of CPAP application seems to ameliorate this antioxidant disturbance only in less severe syndrome.

Conservative management for an esophageal perforation in a patient presented with delayed diagnosis: a case report.

BACKGROUND: Esophageal perforation is a serious condition with a high mortality rate. Successful therapy depends on the size of the rupture; the time elapsed between rupture and diagnosis, and the underlying health of the patient. Common causes of esophageal perforation include medical instrumentation, foreign-body ingestion, and trauma. CASE REPORT: A case of esophageal perforation due to fish bone ingestion in a 67-year-old male is described here, with a review of the pertinent literature. The patient presented with chest pain, fever and right-sided pleural effusion. Initial evaluation was nondiagnostic. The water-soluble contrast swallow test showed no evidence of leakage. Computed tomography scan demonstrated a pneumomediastinum, and right-sided hydropneumothorax. CONCLUSION: The patient was successfully treated using conservative measures.

Conservative management for an esophageal perforation in a patient presented with delayed diagnosis: a case report review of the literature.

Esophageal perforation is a serious condition with a high mortality rate. Successful therapy depends on the size of the rupture; the time elapsed between rupture and diagnosis, and the underlying health of the patient. Common causes of esophageal perforation include medical instrumentation, foreign-body ingestion, and trauma. A case of esophageal perforation due to fish bone ingestion in a 67-year-old male is described here, with a review of the pertinent literature. The patient presented with chest pain, fever and right-sided pleural effusion. Initial evaluation was nondiagnostic. The water-soluble contrast swallow test showed no evidence of leakage. Computed tomography scan demonstrated a pneumomediastinum, and right-sided hydropneumothorax. The patient was successfully treated using conservative measures.

The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis.

Bone metastases occur in 20-40% of patients with lung cancer. Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on lung tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in lung cancer patients with bone metastases. Lung cancer patients (n = 144, Stage IV) with evidence of metastasis bone scan were included. Eighty-seven of 144 experienced bone pain and received ZOL, 4 mg i.v. every 21 days (Group A), whereas the other 57 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of docetaxel 100 mg/m(2) and carboplatin AUC = 6. It was found that Group A had a statistically significant longer survival (p < 0.01) when compared to Group B. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N-telopeptide of type I collagen (NTx) levels decreased in patients with NTx < or = 29 nM BCE/mM creatinine at baseline after treatment with ZOL. The results of our study suggest that the addition of ZOL increases overall survival in lung cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression.

The efficacy of antithrombin administration in the acute phase of burn injury.

Severe burn injury is characterized by the activation of coagulation, decreased fibrinolytic activity and decreased natural anticoagulant activity. The aim of our study was to investigate the effect of antithrombin (AT) administration on coagulation status and on organ function in the early post-burn period. Thirty-one patients were admitted to the burn intensive care unit and were then randomised into two groups (AT-treated and non-AT-treated) for four consecutive days after thermal injury. The clinical data, coagulation and fibrinolysis parameters were compared and the adverse effects were monitored. Significant differences in the time course of coagulation markers (thrombin/AT complexes, tissue plasminogen activator, D-dimer) were observed between AT-treated and non-AT treated groups. According to the International Society on Thrombosis and Haemostasis criteria, disseminated intravascular coagulation (DIC) diagnosis was made in 28 of 31 patients. The presence of overt DIC was associated with mortality (p < 0.001). The Sequential Organ Failure Assessment (SOFA) score time trend differed significantly between the two investigation groups (decreased in the treated group and did not change in the non-AT-treated group). AT-treated patients had an absolute reduction in a 28-day mortality of 25% as compared to the non-AT-treated group (p = 0.004). No treatment related side effects were observed. Treatment with AT seems to affect the coagulation status and reduce multiple organ failure incidence and mortality in the early post-burn period.

Early coagulation disorders after severe burn injury: impact on mortality.

OBJECTIVE: To evaluate the time course of coagulation markers in the early postburn period and clarify the role of coagulation alterations in organ failure and in mortality prognosis. DESIGN AND SETTING: This prospective study was conducted in the burn ICU of a tertiary hospital. PATIENTS: 45 patients with severe thermal burn injury. MEASUREMENTS AND RESULTS: Clinical data and coagulation and fibrinolysis parameters were measured during the first postburn week. The ICU 28-day mortality rate was 33%. Significant differences in the time course of coagulation markers were observed between survivors and nonsurvivors. SOFA score distinguished between patients with overt and nonovert disseminated intravascular coagulation (DIC) during the overall investigation period. Presence of overt DIC was related to mortality (OR=0.1). Antithrombin, protein S, plasminogen activator inhibitor 1, and SOFA score on day 3, protein C on day 5, and thrombin/antithrombin complexes on day 7 revealed a good prognostic value for ICU mortality, according to the area under ROC curves. CONCLUSIONS: Severe thermal injury is associated with the early activation of coagulation cascade, presence of DIC, organ failure, and increased mortality.

Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis?

OBJECTIVE: To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients. DESIGN AND SETTING: Prospective, observational study in a four bed Burn Intensive Care Unit. PATIENTS: Forty-three patients admitted in a Burn ICU were included in our study. MEASUREMENTS AND RESULTS: Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT. CONCLUSIONS: Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.

Epstein-Barr virus DNA in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is the most common idiopathic interstitial pneumonia. The human herpesviruses and especially Epstein-Barr virus have been implicated in the etiology of idiopathic pulmonary fibrosis in a number of studies. AIM: The aim of this study was to investigate the potential association between idiopathic pulmonary fibrosis and Epstein-Barr virus. METHODS: Bronchoalveolar lavage fluid and sera were collected from 63 patients out of whom 17 suffered of idiopathic pulmonary fibrosis and 46 of other interstitial lung diseases. Sera from 50 healthy, age-matched individuals were also collected. Antibodies to the early, nuclear, and capsid antigens of Epstein-Barr virus were determined by enzyme immunoassay and indirect immunofluorescence. Additionally polymerase chain reaction was performed in bronchoalveolar lavage fluid in order to investigate the presence of Epstein-Barr virus DNA. Positive polymerase chain reaction results were confirmed by nucleotide sequencing. RESULTS: Statistically significant differences were observed in the frequency of IgA antibodies to viral capsid antigen among patients with idiopathic pulmonary fibrosis, patients with other interstitial lung diseases and healthy controls (60%, 24.4% and 22% respectively, p = 0.013). Epstein-Barr virus DNA was detected in the bronchoalveolar lavage fluid of 3 patients with idiopathic pulmonary fibrosis but in none of the patients with other diseases (p = 0.024). CONCLUSIONS: The results of this study support the association between IPF and EBV, at least in some cases, and provide evidence that BALF is an alternative for the detection of viral DNA in patients with IPF. However further investigation is required concerning the etiology of idiopathic pulmonary fibrosis.

Variations in alveolar cell populations, lymphocyte subsets and NK-cells in different stages of active pulmonary sarcoidosis.

BACKGROUND: The type and mode of presentation of pulmonary sarcoidosis (radiologic stage, activity) influence alveolar lymphocyte number and subsets as well as other inflammatory cells. AIM: To investigate the variations in alveolar cells, lymphocyte subsets and NK-cells in different radiological stages of active pulmonary sarcoidosis. METHODS: 85 untreated, newly diagnosed patients (32 male, 53 female), median age 47.2+/-14.7 years were investigated. Patients were classified into chest x-ray stages (33 stage I, 27 stage II, 14 stage III and 11 stage IV disease). Bronchoalveolar lavage was performed with 4 portions of 50 mL. Total cells and cell differentials were counted, while CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK-cells) and CD3+CD16/56+ (NKT-cells) were determined by flow cytometry. RESULTS: Lymphocytosis was high in all stages. Significant differences were found in: a) CD4 between stages I and II and I and IV. b) CD8 between stages I and IV and c) NK and NKT cells between stages I and III. CONCLUSIONS: Variations were observed in alveolar cells and lymphocyte subsets in different stages of pulmonary sarcoidosis. Cells exhibiting cytotoxic activity were increased with stage progression, CD8 from stage I to IV, NK and NKT cells from stage I to III. These cells may be involved in the inflammatory process regulating granuloma formation.