Serum Vitamin D Concentration and Markers of Bone Metabolism in Perimenopausal and Postmenopausal Women with Asthma and COPD.

Aging and menopause are closely related to hormonal and metabolic changes. Vitamin D is a crucial factor modulating several metabolic processes. The aim of this study was to evaluate biomarkers of bone metabolism in peri- and postmenopausal women with obstructive lung diseases. Sixty two female patients, 27 with asthma and 35 with COPD, aged over 45 years (median age 58 and 64 years, respectively) were enrolled into the study. The evaluation included lung function, bone mineral density, serum concentration of vitamin D, and bone metabolism markers. The study groups differed significantly in terms of forced expiratory volume in 1 s (FEV1); median values of 1.79 L vs. 1.16 L (p = 0.0001) and 71.2% vs. 53.0% predicted (p = 0.0072) and in vitamin D concentration (12.3 ng/ml vs. 17.6 ng/ml). Total bone mineral density (BMD) was lower in the COPD group (p = 0.0115). Serum vitamin D inversely correlated with the number of pack-years in asthma patients (r = -0.45, p = 0.0192). There was no correlation between serum vitamin D and disease duration or severity, and the Asthma Control Test (ACT) and the modified Medical Research Council (mMRC) dyspnea scores. The serum bone metabolism markers C-terminal cross-linked telopeptide of collagen type I (BCROSS), N-terminal propeptides of procollagen type-1 (tP1NP), and N-mid osteocalcin (OCN) inversely correlated with age in the COPD, but not asthma, patients (r = -0.38, p = 0.0264; r = -0.37, p = 0.0270; and r = -0.42, p = 0.0125, respectively). We conclude that peri- and postmenopausal women with obstructive lung diseases had a decreased serum concentration of vitamin D. Furthermore, vitamin D and body mineral density were appreciably lower in women with COPD than those with asthma.

Metabolic Syndrome as a Factor Affecting Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a systemic disease which may be associated with other comorbidities. The aim of the study was to estimate the incidence of metabolic syndrome (MS) in COPD patients and to assess its impact on systemic inflammation and lung function. MS was diagnosed in accordance with the recommendations of the Polish Forum for the Prevention of Cardiovascular Diseases. The study group consisted of 267 patients with stable COPD in all stages of severity. All patients underwent spirometry with bronchial reversibility testing and 6 min walk test (6MWT). The following blood tests were evaluated: lipid profile, glucose and C-reactive protein as well as serum concentration of IL-6, leptin, adiponectin, and endothelin. MS was diagnosed in 93 patients (35.8%). No differences were observed in the incidence of MS in relation to airflow limitation severity (mild; moderate; severe and very severe: 38.9; 36.3; 35.2 and 25.0%, respectively). FEV1 (% predicted), FVC (% predicted), 6MWT distance (6MWD), age, and the number of pack-years were similar in patients with and without MS. MS was more frequent in males than females (38.7 vs. 28.4%, p > 0.05). Serum concentrations of IL-6, endothelin, leptin, and CRP were higher in the MS group, contrary to adiponectin concentration which was lower (p < 0.01). MS was more frequent in male COPD patients, but there were no differences in its frequency between patients with different severity of airflow limitation. We conclude that MS, as a comorbidity, occurs in all COPD stages and affects systemic inflammation. MS incidence does not depend on COPD severity.

Exacerbations of Chronic Obstructive Pulmonary Disease and Quality of Life of Patients.

Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the most important factors which influence the course of disease and quality of life in COPD patients. The aim of the study was to assess the exacerbation frequency in COPD patients in relation to COPD severity and to evaluate the impact of the number of exacerbations on quality of life. The study included 445 COPD patients in all four progressive stages of the disease according to GOLD classification. The patients recorded exacerbations in diaries. Spirometry, St. George's Respiratory Questionnaire, and dyspnea score were assessed at baseline and after 12 and 24 months from enrollment. After 24 months, 261 diaries were returned. The mean number of exacerbations per year in the sequential GOLD 1-4 stages of COPD was as follows: 1.3 ± 2.1, 1.4 ± 2.0, 1.7 ± 1.8, and 3.4 ± 4.5. A statistical difference in the exacerbation frequency was noted for GOLD 4 and the remaining groups. A significant negative correlation was found between the number of exacerbations and functional status for GOLD 2 and 3 stages. We conclude that the number of exacerbations is the highest in the most severe stage of the disease. The quality of life of patients with moderate and severe COPD correlates negatively with the number of exacerbations.

Thyroid Hormone Levels and TSH Activity in Patients with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) is characterized by complete cessation of inspiratory flow (apnea) or upper airway airflow limitation (hypopnea) with increased respiratory muscle activity, which is repeatedly observed during sleep. Hypothyroidism has been described as a rare cause of OSAS, but it is considered to be the main cause of breathing disorders during sleep in patients in whom an improvement of OSAS is observed after thyroid hormone replacement therapy. Nevertheless, euthyreosis due to thyroxine replacement in patients with OSAS often does not improve the breathing disorder and treatment with continuous positive airway pressure is usually applied. The aim of this study was to assess thyroid function in patients with OSAS. We studied 813 patients in whom severe OSAS was diagnosed; the mean apnea-hypopnea index was 44.0. Most of the patients were obese (mean BMI 33.1 ± 6.6 kg/m2) and had excessive daytime sleepiness (ESS 12.8 ± 6.6). With the thyroid stimulating hormone (TSH) concentration as the major criterion, hypothyroidism was diagnosed in 38 (4.7%) and hyperthyroidism was diagnosed in 31 (3.8%) patients. Analysis of basic anthropometric data, selected polysomnography results, and TSH, fT3, and fT4 values did not reveal any significant correlations. In conclusion, the incidence of thyroid function disorders seems to be no different in OSAS than that in the general population. We did not find correlations between TSH activity and the severity of breathing disorders during sleep.

Prevalence of Pulmonary Infections Caused by Atypical Pathogens in non-HIV Immunocompromised Patients.

Although atypical bacteria are important causes of lower airway infections, data on their role in immunocompromised patients are scarce. The aim of the study was to evaluate the prevalence of atypical pulmonary infections in patients with various types of immunosuppression, and to analyze clinical characteristics of these infections. Eighty non-HIV immunocompromised patients with different underlying diseases and clinical and radiological signs of pulmonary infection were enrolled. Due to incomplete data on eight patients, 72 patients were eligible for final analysis (median age 58 years). All patients underwent fiberoptic bronchoscopy and bronchoalveolar lavage. Bronchoalveolar lavage fluid (BALF) fluid samples were sent for direct microscopy, cultures, and fungal antigen detection, when appropriate. Commercial qualitative amplification assay (PNEUMOTRIS oligomix Alert Kit(®)), based on nested PCR method, was used to detect specific DNA sequences of L. pneumophila, C. pneumoniae, and M. pneumoniae in BALF. There were 61 (84.7 %) patients with hematologic diseases, 3 (4.2 %) after solid organ transplantation, and 8 (11.1 %) with miscellaneous diseases affecting immune status. Specific sequences of M. pneumoniae, C. pneumoniae, and L. pneumophila DNA were found in 7 (9.7 %), 2 (2.8 %), and 0 patients, respectively. In 8 of these patients co-infections with different microorganisms were demonstrated. Co-infection with A. baumanii and P. aeruginosa was diagnosed in three patients who died. We conclude that atypical lower airway infections are uncommon in immunocompromised patients. The majority of these infections are co-infections rather than single pathogen infections.

Comparison of Small Bore Catheter Aspiration and Chest Tube Drainage in the Management of Spontaneous Pneumothorax.

Beside standard chest tube drainage other less invasive techniques have been used in the management of patients with an acute episode of spontaneous pneumothorax. The aim of the study was to evaluate the short term effect of spontaneous pneumothorax treatment with small-bore pleural catheter and manual aspiration as compared to large-bore chest tube drainage. Patients with an episode of pneumothorax who required pleural intervention were enrolled in the study and randomly assigned to one of the treatment arms: (1) small-bore pleural catheter (8 Fr) with manual aspiration; (2) standard chest tube drainage (20-24 Fr). Success rate of the first line treatment, duration of catheter or chest tube drainage, and the need for surgical intervention were the outcome measures. The study group included 49 patients (mean age 46.9±21.3 years); with 22 and 27 allocated to small bore manual aspiration and chest tube drainage groups, respectively. There were no significant differences in the baseline characteristics of patients in both therapeutic arms. First line treatment success rates were 64% and 82% in the manual aspiration and chest tube drainage groups, respectively; the difference was insignificant. Median time of treatment with small bore catheter was significantly shorter than conventional chest tube drainage (2.0 vs. 6.0 days; p<0.05). Our results show that treatment of spontaneous pneumothorax with small-bore pleural catheter and manual aspiration might be similarly effective as is chest tube drainage in terms of immediate lung re-expansion.

Development and Evaluation of the New Predictive Models in Tuberculous Pleuritis.

Different pleural fluid biomarkers have been found useful in the discrimination between tuberculous pleural effusion (TPE) and non-TPE, with interferon gamma (IFN-γ) showing the highest single marker diagnostic accuracy. The aim of the present study was to develop predictive models based on clinical data and pleural fluid biomarkers, other than IFN-γ, which could be applied in differentiating TPE and non-TPE. Two hundred and forty two patients with newly diagnosed pleural effusion were prospectively enrolled. Upon completion of the diagnostic procedures, the underlying disease was identified in 203 patients (117 men and 86 women, median age 65 years; 44 patients with TPE and 159 with non-TPE) who formed the proper study group. Pleural fluid level of ADA, IFN-γ, IL-2, IL-2sRα, IL-12p40, IL-18, IL-23, IP-10, Fas-ligand, MDC, and TNF-α was measured and then ROC analysis and multivariate logistic regression were used to construct the predictive models. Two predictive models with very high diagnostic accuracy (AUC > 0.95) were developed. The first model included body temperature, white blood cell count, pleural fluid ADA and IP-10. The second model was based on age, sex, body temperature, white blood cell count, pleural fluid lymphocyte percentage, and IP-10 level. We conclude that two new predictive models based on clinical and laboratory data demonstrate very high diagnostic performance and can be potentially used in clinical practice to differentiate between TPE and non-TPE.

Diagnostic performance of different pleural fluid biomarkers in tuberculous pleurisy.

Due to the paucibacillary nature of tuberculous pleural effusion the diagnosis of pleural tuberculosis is challenging. This prospective study was undertaken to evaluate the diagnostic performance of ten different pleural fluid biomarkers in the differentiation between tuberculous and non-tuberculous pleural effusions. Two hundred and three patients with pleural effusion (117 men and 86 women, median age 65 years) were enrolled. Routine diagnostic work-up, including thoracentesis and pleural fluid analysis, was performed to determine the cause of pleural effusion. The following biomarkers were measured in pleural fluid: adenosine deaminase (ADA), interferon gamma (IFN-γ), interleukin 2 soluble receptor (IL-2sRα), sub-unit p40 of interleukin 12b (IL-12p40), interleukin 18 (IL-18), interleukin 23 (IL-23), IFN-γ induced protein 10 kDa (IP-10), Fas-ligand, human macrophage-derived chemokine (MDC) and tumor necrosis factor alfa (TNF-α). There were 44 (21.7%) patients with tuberculous pleural effusion, 88 (43.3%) patients with malignant pleural effusion, 35 (17.2%) with parapneumonic effusion/pleural empyema, 30 (14.8%) with pleural transudates, and 6 (3%) with miscellaneous underlying diseases. Pleural fluid IFN-γ was found the most accurate marker differentiating tuberculous from non-tuberculous pleural effusion, with sensitivity, specificity, PPV, NPV, and AUC 97%, 98%, 95.5%, 99.4%, and 0.99, respectively. Two other biomarkers (IP-10 and Fas ligand) also showed very high diagnostic accuracy with AUC≥0.95. AUC for ADA was 0.92. We conclude that IFN-γ, IP-10, and Fas-ligand in pleural fluid are highly accurate biomarkers differentiating tuberculous from non-tuberculous pleural effusion.

Variability of Transcutaneous Oxygen and Carbon Dioxide Pressure Measurements Associated with Sensor Location.

Transcutaneous measurement of oxygen and carbon dioxide pressure (PtcO2 and PtcCO2) is useful in gas exchange monitoring. However, the relationship between PtcO2, pulse oximetry (SaO2) and arterial blood gases (ABG) is unclear. The aim of the present study was to compare PtcO2 and PtcCO2 with SaO2 and ABG, to evaluate the effect of sensor location on the results and stability of PtcO2 and PtcCO2, and to assess the impact of body composition on PtcO2 and PtcCO2. PtcO2 and PtcCO2 were measured in 20 healthy volunteers at three locations: right second intercostal space, lateral surface of the abdomen, and the inner surface of the left arm. The results were recorded 10, 15, and 20 min after sensor fixation and compared with SaO2 and ABG measured 20 min after electrode placement on the chest. Body composition was evaluated by bioimpedance. The findings were that PtcO2 was stable on the chest; but on the arm and abdomen it increased and reached maximum at 20 min. Transcutaneous PCO2 stabilized at 10 min in all the three locations. No significant correlations between PtcO2 and SaO2 or PaO2 were found. Transcutaneous PCO2 correlated with PaCO2. Both PtcO2 and PtcCO2 were not influenced by body composition. We conclude that the value of PtcO2 in monitoring of blood oxygenation was not unequivocally confirmed; PtcCO2 reliably reflects PaCO2, irrespective of sensor location. Body composition does not affect PtcO2 and PtcCO2.

Influence of denture plaque biofilm on oral mucosal membrane in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have the lower airways colonized with pathogenic bacteria in a stable period of the disease and during exacerbations. The etiology of bacterial exacerbations of COPD depends on the underlying disease, the frequency of exacerbations and antibiotic therapy. Microorganisms can be aspirated off the denture plaque biofilm into the lower respiratory tract and could reduce the patient's immunity and cause pneumonia. COPD patients, who are using acrylic dentures in oral cavity, are exposed to denture stomatitis and oral candidiasis. The aim of this study was to establish the composition of denture plaque biofilm and its impact on the oral mucosa in COPD patients. The study included patients in a stable phase of COPD using removable denture and the control group included healthy wearer's appliances. Examinations concerned the oral mucosal membrane and the hygienic condition of prosthetic restorations. Microbiological examinations were performed by taking a direct swab from the surface of acrylic dentures. Seventeen bacterial and fungal strains were isolated from denture plaque of COPD patients, which could be a reservoir of pathogens in the upper and lower airways. The results showed a greater frequency of prosthetic stomatitis complicated by mucosal infections among COPD patients compared to healthy subjects.

The Prevalence of Oral Inflammation Among Denture Wearing Patients with Chronic Obstructive Pulmonary Disease.

Oral inflammation is an important contributor to the etiology of chronic obstructive pulmonary disease, which can impact patient's health status. Previous studies indicate that people with poor oral health are at higher risk for nosocomial pneumonia. Denture wearing is one promoting factor in the development of mucosal infections. Colonization of the denture plaque by Gram-negative bacteria, Candida spp., or other respiratory pathogens, occurring locally, may be aspirated to the lungs. The studies showed that chronic obstructive pulmonary disease (COPD) patients treated with combinations of medicines with corticosteroids more frequently suffer from Candida-associated denture stomatitis. Treatment of oral candidiasis in patients with COPD constitutes a therapeutic problem. Therefore, it is essential to pay attention to the condition of oral mucosal membrane and denture hygiene habits. The guidelines for care and maintenance of dentures for COPD patients are presented in this paper. The majority of patients required improvement of their prosthetic and oral hygiene. Standard oral hygiene procedures in relation to dentures, conducted for prophylaxis of stomatitis complicated by mucosal infection among immunocompromised patients, are essential to maintain healthy oral tissues. The elimination of traumatic denture action in dental office, compliance with oral and denture hygiene, proper use and storage of prosthetic appliances in a dry environment outside the oral cavity can reduce susceptibility to infection. Proper attention to hygiene, including brushing and rinsing the mouth, may also help prevent denture stomatitis in these patients.

Causes of Chronic Cough in Non-smoking Patients.

Chronic cough is a common medical problem. The aim of the study was to analyze chronic cough causes in non-smoking patients and to search for demographic factors associated with different cough reasons. The etiology of cough was determined by medical history, diagnostic tests and response to specific treatment. Patients with significant abnormalities in the chest radiograph or spirometry were not included. The study included 131 non-smoking patients; median age 54 years, 77 % female. The most frequent causes of cough were gastroesophageal reflux disease (GERD) (62 %) and upper airway cough syndrome (UACS) (46 %). Cough variant asthma and non-asthmatic eosinophilic bronchitis (NAEB) were diagnosed in 32 (25 %) and 19 (15 %) patients, respectively. Other cough causes were found in 27 patients (21 %). Asthma was a significantly more common cause of chronic cough in women than in men (31 % vs. 3 %, p = 0.005). A reverse relationship was demonstrated for UACS (39 % vs. 67 %, p = 0.01). Patients with chronic cough aged >50 yrs were more likely to be diagnosed with less common cough causes. In conclusion, the most common chronic cough reasons are GERD and UACS. Asthma-related cough is diagnosed more frequently in females, while UACS-related cough is more frequent in males.

Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate.

Carboxylesterase 1 is the enzyme involved in methylphenidate (MPH) metabolism. The aim of this study was to evaluate the association between a -75 T>G polymorphism and appetite reduction in children with attention-deficit/hyperactivity disorder (ADHD). A sample of 213 children with ADHD was investigated. The primary outcome was appetite reduction measured by the Barkley Stimulant Side Effect Rating Scale applied at baseline, at 1 and 3 months of treatment. MPH doses were augmented until no further clinical improvement or significant adverse events occurred. The G allele presented a trend for association with appetite reduction scores (P=0.05). A significant interaction between the G allele and treatment over time for appetite reduction scores was also observed (P=0.03). The G allele carriers presented a higher risk for appetite reduction worsening when compared with T allele homozygotes (odds ratio=3.47, P=0.01). The present results suggest an influence of carboxylesterase 1 -75 T>G polymorphism on the worsening of appetite reduction with MPH treatment in youths with ADHD.

CD4+/CD25+ cells in systemic inflammation in COPD.

The autoimmune reaction is recently suspected to play a role in the pathogenesis of chronic obstructive lung disease (COPD). As COPD is a systemic disease, the elements of an autoimmune response in circulatory system is of interest. It has been shown that regulatory T cells are important in the control of autoimmunity. There are some data on a role of adiponectin in the regulation of immune reactions. The objective of this study was to assess the elements of autoimmune reaction in the peripheral blood (PB) of patients with COPD. Twenty-eight patients with mild/moderate COPD and 20 healthy volunteers were investigated. Flow cytometry method with mixtures of monoclonal antibodies anti: CD14/CD45, CD3/CD19, CD4/CD25/CTLA4 and CD8/CD25 were used. Concentration of adiponectin was measured using ELISA method. We observed significantly lower proportion of CD4+/CD25+ as well as CD4+/CD25+ (high) cells in COPD patients than in healthy controls (15.3 versus 17.8% and 0.79 versus 1.54%, respectively, P < 0.05). The proportion of CTLA4+ cells in CD25+ cells and the mean fluorescence of CTLA4 on CD4+ cells were higher in patients than in healthy controls (10.4 versus 4.7%, P < 0.05, 189% versus 149%, non significant, respectively). We found significantly elevated concentration of adiponectin in patients when compared to healthy subjects (15.4 versus 8.5 µl/ml, P < 0.05). We found that the adiponectin/BMI ratio correlated with the decrease of FEV(1) %. The results of this study support the possible role of CD4/CD25/CTLA4 cells and adiponectin in the systemic inflammation in COPD.

Incidence and aetiology of eosinophilic pleural effusion.

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia. A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed. We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (< or =40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample. Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.

Nontuberculous mycobacterial infections among patients suspected of pulmonary tuberculosis.

The purpose of this study was to present a retrospective analysis of the frequency of nontuberculous mycobacteria (NTM)-related pulmonary infections among the AFB-positive and/or culture-positive patients in the Warsaw region who were suspected of tuberculosis (TB) and hospitalized in the university hospital between 1999 and 2005. All the AFB-positive pulmonary samples were examined with a molecular method using the Amplicor MTB test (Roche) for detection of Mycobacterium tuberculosis complex, and all mycobacterial isolates were speciated by high performance liquid chromatography (HPLC) analysis of mycolic acids. Patients who met clinical, radiological, and bacteriological criteria of mycobacteriosis were classified according to the American Thoracic Society (ATS) guidelines for diagnosis of NTM related disease. Among the 445 smear-positive or/and culture-positive patients, 142 subjects (31.9%) were found to be infected with M. tuberculosis. Among 303 non-TB patients, mycobacteriosis was found in 27 (8.9%) subjects. The frequency of NTM-related lung disease as compared to the bacteriologically-confirmed lung TB was estimated at 1:5. The rapid, precise methods of NTM speciation are necessary for progress in diagnostics of NTM related diseases.

Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease.

UNLABELLED: Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. AIM: To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness of bronchial walls assessed by high resolution computed tomography (HRCT) in asthma and COPD patients. MATERIAL AND METHODS: The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 +/- 10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 +/- 9 years). In all subjects lung function tests and HRCT scanning of the chest were performed. External (D) and internal (L) diameters of the airways were assessed at five selected lung levels. The lumen area (A(L)), wall area (WA), wall thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated. Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). Total and differential cell counts were assessed in the BAL fluid. RESULTS: Mean FEV(1)% pred was 80 +/- 19%, and 73 +/- 20% in asthma and COPD patients, respectively (NS). No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD. There were no significant differences in the airway diameter or airway wall thickness. The mean inner airway diameter was 1.4 +/- 0.3 and 1.2 +/- 0.3 mm and the mean lumen area was 1.8 +/- 0.7 and 1.6 +/- 0.7 mm(2) in asthma and COPD, respectively (NS). Negative correlations between the eosinophil count in BALF and inner airway diameter (r=-0.7, P<0.05) and lumen area (r=-0.7, P<0.05) were found in asthmatics. There was no significant relationship between the BALF cell count and airway wall thickness in COPD patients. - CONCLUSIONS: In mild-to-moderate asthma and COPD the airway diameter and thickness are similar. In asthmatics, the airway diameter might be associated with eosinophil count in BAL fluid.

Diagnostic utility of pleural fluid and serum markers in differentiation between malignant and non-malignant pleural effusions.

STUDY OBJECTIVE: To evaluate the diagnostic value of four different tumor markers: cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and neuron specific enolase (NSE) in patients with malignant and non-malignant pleural effusion. MATERIAL AND METHODS: One hundred and two patients with pleural effusion treated in the University Hospital in Warsaw between 2001 and 2003 were studied. They underwent an extensive, diagnostic work-up in order to determine the pleural effusion etiology. Patients with known pleural fluid etiology were labeled as the study group and submitted for further analysis. Pleural fluid and serum samples for CA-125, CEA, CYFRA 21-1 and NSE measurements were collected during the first thoracentesis, centrifuged, and frozen until further use. Pleural fluid and serum concentration of tumor markers were assessed by electrochemiluminescence methods using commercial kits. RESULTS: 74 patients (32 M, 42 F; mean age 65 +/-14 years) composed the final study group. Exudative pleural effusion was found in 62 patients; of these 36 were malignant (48.6% of all effusions), 20 parapneumonic (or pleural empyema), and 6 tuberculous. In 12 patients, pleural transudate was diagnosed. The highest diagnostic sensitivity for malignant pleural effusion was found for NSE (94.4% and 80.6% in the pleural fluid and serum, respectively). However, the specificity of NSE measurement was relatively low (36.1% and 47.4% in pleural fluid and serum, respectively). The most specific markers of malignant pleural fluid etiology were pleural fluid CYFRA 21-1 and CEA levels (92.1% and 92.1%, respectively). CA-125 was found to be the most specific serum marker of pleural malignancies (78.9%). The AUC for combined pleural markers was 0.89, combined serum markers 0.82, combined ratio pleural/serum markers 0.88. CONCLUSIONS: There are significant differences between the diagnostic value of various pleural fluid and serum markers. Overall, pleural fluid markers are superior to serum markers in determining the pleural fluid etiology. A combination of two or more tumor markers may help improve their diagnostic accuracy. Pleural fluid and serum measurements of different tumor markers play a limited role in the differentiation between malignant and non-malignant pleural effusions.

Exercise capacity in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common disease characterized by repetitive partial or complete closure of the upper airway during sleep. Cardiovascular disturbances are the most important complications responsible for increased morbidity and mortality. It is suggested that daytime somnolence, chronic fatigue, and nocturnal hypoxemia may further impair muscle function and decrease exercise fitness. The aim of this study was to evaluate cardiopulmonary response to exercise in OSAS patients. One hundred and eleven middle aged (50.2+/-10 yr), obese (BMI 31.0+/-4.6 kg/m2) patients (109 M, 2F) with severe OSAS (AHI 47.2+/-23.1 h(-1)) were enrolled into the study. OSAS was diagnosed with overnight polysomnography and a symptom-limited cardiopulmonary exercise test was performed on a treadmill using Bruce protocol. The results showed that the most frequent reason for exercise termination were: muscle fatigue and/or dyspnea (66+/-), increase in systolic blood pressure>220 mmHg (20%), ECG abnormalities, and chest pain (6%). Although the mean VO2 peak was within the reference value (29.6+/-6 mlO2/kg/min), in 52 patients (46%) VO2 peak was <84% of predicted. Hypertensive response to exercise was diagnosed in 39 of patients (35%). Patients with severe sleep apnea (AHI40>or=h(-1)) were characterized by higher mean blood pressure at rest, at 25%, 50% of maximal work load, at peak exercise and at post-exercise recovery. Several significant correlations between hemodynamic responses to exercise and sleep apnea severity were also noted. We conclude that exercise tolerance can be limited due to hypertensive response in about 20% of patients. Patients with severe OSAS have exaggerated hemodynamic response to exercise and delayed post-exercise blood pressure recovery. Cardiopulmonary response to exercise seems to be related to sleep apnea severity.

Effect of IFN-gamma stimulation on expression of intercellular adhesion molecule-1 (ICAM-1) on alveolar macrophages in patients with non-small cell lung cancer.

An impairment of in vitro cytotoxicity and tumoricidal function of alveolar macrophages (AMs) in patients with lung cancer was reported in a number of studies. The aim of our study was to evaluate the expression of intercellular adhesion molecule-1 (ICAM-1) on AMs after stimulation with interferon-gamma (IFN-gamma) in patients with non-small cell lung cancer (NSCLC). The study was performed in 13 patients with NSCLC, 6 patients with various nonmalignant pulmonary diseases, and 6 healthy volunteers. AMs were isolated from bronchoalveolar lavage fluid (BALF) by adherence and then cultured with or without IFN-gamma for 24 h. The expression of ICAM-1 on AMs was analyzed by flow cytometry. Stimulation with IFN-gamma caused increased expression of ICAM-1 on AMs in all studied groups (p < 0.05). The degree of the increase in ICAM-1 expression on AMs after IFN-gamma stimulation was significantly lower in patients with NSCLC compared with healthy volunteers (p = 0.002) or the other patients (p = 0.022). The results suggest impaired reactivity of ICAM-1 expression on AMs after stimulation with IFN-gamma in patients with NSCLC, which might be involved in functional defects of AMs in patients with NSCLC.