Abstract: Eur J Clin Invest 2010; 41 (1): 30-38 ABSTRACT: Background  Obesity and asthma are characterized by the presence of inflammation. Leptin and adiponectin are circulating hormones produced by adipose tissue that regulate several metabolic and inflammatory functions. We aimed to determine whether obesity influences asthmatic inflammation as well as the contribution of leptin or/and adiponectin to a possible linkage between asthmatic and obesity-related inflammation. Materials and methods  One hundred patients with asthma and 60 healthy controls were studied. Subjects who had a comorbid illness that could interfere with the proposed tests were excluded. All subjects were divided into three groups (normal range, pre-obese, obese) according to the criteria of the current WHO international classification for body mass index (BMI). Possible associations between variables expressing airway inflammation, bronchial hyper-responsiveness, systemic inflammation and obesity, as assessed by BMI, were evaluated. Leptin and adiponectin were also measured and were associated with asthma airway and systemic inflammatory variables to elucidate possible associations. Results  Obese patients had significant higher values of LTE(4) /creatinine in urine compared with pre-obese and normal range ones. In a linear regression model, the only significant associations were those between BMI and LTE(4) /creatinine in urine. Using the same model, log leptin and log adiponectin presented positive and negative associations, respectively with LTE(4) /creatinine in urine. No other significant associations were observed in both patients and healthy subjects. Conclusions  In a selected cohort of asthmatic patients, obesity is significantly associated with increased urinary leukotriene levels. Alterations of leptin/adiponectin balance may be related to the presence of leukotriene inflammation in obese asthmatic patients.
Abstract: The aim of this paper is to study the prevalence of Raynaud's phenomenon in young males. Young males were examined prospectively in a district hospital, and laboratory tests were performed on the basis of the clinical history. Young males (3.912), age 18-28Â years old, were examined. Raynaud's phenomenon was present in seven men (1,79 per 1.000, 95% CI 0.72-3.68). Three of them had at least one member in their family diagnosed with Raynaud's phenomenon. Three were smokers. All had negative immunological test. Five patients reported having severe attacks and two had only mild ischemic attacks. The treatment was conservative for all patients, two of them necessitated vasodilators. Very low prevalence of Raynaud's phenomenon was observed in this young male group compared with the previous studies.
Abstract: OBJECTIVES: To correlate serum levels of bone markers with pain levels and extent of skeletal disease (EOD), in patients suffering from prostate cancer with bone only metastases. METHODS: Thirty-six males with hormone-refractory prostate carcinoma, bone only metastases and no history of therapies, drugs, or diseases that affect bone metabolism were studied. Karnofsky performance status, pain scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of type I collagen were analysed. Twenty-four healthy controls of the same age were also established. RESULTS: With only the exception of OC, bone marker values of patients were significantly increased compared with the upper reference limits (P<0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal telopeptide of type I collagen). All bone markers and prostate-specific antigen also showed significant paired correlations (P < or = 0.019) and linear increases with advancing EOD (P < or = 0.032). Finally, none of the measured markers correlated significantly with pain levels. CONCLUSION: Bone markers are remarkably elevated in the serum of prostate cancer patients with metastatic bone disease and correlate with EOD. Paired correlations also suggest an accelerated but proportional (coupled) bone metabolism.
Abstract: To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with (186)Re-1,1-hydroxyethylidene diphosphonate ((186)Re-HEDP).
Abstract: BACKGROUND: Various systemic inflammatory markers have been evaluated for their value in acute exacerbations of chronic obstructive pulmonary disease (COPD). Leptin and adiponectin have been linked to acute exacerbations and stable COPD. OBJECTIVES: To assess plasma leptin, adiponectin and their ratio in acute exacerbations of COPD and to study possible associations with inflammatory biomarkers. METHODS: Plasma leptin, adiponectin and their ratio (L/A) and serum biomarkers of systemic inflammation C-reactive protein (CRP), Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were assessed at three time points (admission, resolution and stable phase - 8 weeks after resolution) in a selected cohort of 63 COPD patients hospitalized for acute exacerbations. Subjects with comorbidities related to adipose tissue hormones were meticulously excluded. MEASUREMENTS AND MAIN RESULTS: All systemic inflammatory biomarkers, leptin and L/A ratio were elevated during admission compared to resolution and stable phase (mean L/A ratio 2.6 vs. 1.57 vs. 1.22, respectively; p<0.0001), whereas adiponectin was elevated at resolution compared to admission. Log leptin, adiponectin and L/A ratio were significantly associated with variables of systemic inflammation, after proper adjustments, both on admission and in stable condition. In stepwise multiple linear regression models, IL-6 and TNF-alpha present the most significant associations with leptin, adiponectin and their ratio. CONCLUSIONS: Our data suggest that both leptin and adiponectin are associated with the systemic inflammatory process during exacerbations of COPD. The most significant associations seem to be those with IL-6 and TNF-alpha.
Abstract: Pityriasis rosea is an acute self-limiting dermatosis with clinical and epidemiological features that suggest viral involvement. The aim of this study was to investigate a possible association between pityriasis rosea and human herpesvirus 8 (HHV-8). Lesional skin tissue was obtained from 34 Kaposi's sarcoma-negative, immunocompetent patients with typical acute phase pityriasis rosea. Nested polymerase chain reaction with specific primer for HHV-8 DNA sequences was performed and all positive results were confirmed by sequencing. Seven out of 34 lesional skin specimens (20.5%) were found to be positive for the HHV-8 genome. All the positive samples were confirmed by DNA sequencing. We conclude that, in some cases, HHV-8 is implicated the pathogenesis of pityriasis rosea.
Abstract: BACKGROUND: Collection of exhaled breath condensate (EBC) is a safe, non-invasive method to collect droplets of the airway surface liquid and measure mediators of airway inflammation and oxidative stress, such as cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane. OBJECTIVE: The aim of our study was to investigate baseline values of inflammatory lipid mediators in EBC and their relation to asthma severity. METHODS: Nineteen healthy subjects, 16 mild, 12 moderate and 15 severe asthmatics were studied. All subjects attended a clinic visit for spirometry and EBC collection. The concentrations of exhaled cys-LTs and 8-isoprostane were measured by means of specific enzyme immunoassays. RESULTS: 8-isoprostane levels were significantly increased in mild (49.1+/-5.2 pg/mL, p<0.001), moderate (49.7+/-5.2 pg/mL, p<0.001) and severe asthmatics (77.7+/-7.3 pg/mL, p<0.001), compared to healthy controls (16.4+/-1.6 pg/mL). Moreover, 8-isoprostane levels were significantly higher in severe compared to mild and moderate asthmatics (p<0.01). Cys-LT levels were significantly higher in moderate (34.6+/-4.4 pg/mL, p<0.05) and severe asthmatics (47.9+/-6.0 pg/mL, p<0.001), while no significant difference was found between healthy controls and mild asthmatics. 8-isoprostane levels in EBC of asthmatics strongly correlated with cys-LT levels (r=0.61, p<0.0001). CONCLUSIONS: 8-isoprostane and cys-LT are detectable in EBC of healthy subjects and their levels progressively increase in asthmatic patients according to disease severity. The correlation found between these two lipid mediators indicating a link between oxidative stress and airway inflammation.
Abstract: We present a detailed dynamic light scattering study of the phase separation in the ocular lens emerging during cold cataract development. Cold cataract is a phase separation effect that proceeds via spinodal decomposition of the lens cytoplasm with cooling. The intensity autocorrelation functions of the lens protein content are analyzed with the aid of two methods, providing information on the populations and dynamics of the scattering elements associated with cold cataract. It is found that the temperature dependence of many measurable parameters changes appreciably at the characteristic temperature approximately 16+/-1 degrees C which is associated with the onset of cold cataract. By extending the temperature range of this work to previously inaccessible regimes, i.e., well below the phase separation or coexistence curve at Tcc, we have been able to accurately determine the temperature dependence of the collective and self-diffusion coefficients of proteins near the spinodal. The analysis showed that the dynamics of proteins bears some resemblance to the dynamics of structural glasses, where the apparent activation energy for particle diffusion increases below Tcc, indicating a highly cooperative motion. Application of ideas developed for studying the critical dynamics of binary protein-solvent mixtures, as well as the use of a modified Arrhenius equation, enabled us to estimate the spinodal temperature Tsp of the lens nucleus. The applicability of dynamic light scattering as a noninvasive, early-diagnostic tool for ocular diseases is also demonstrated in light of the findings of the present paper.
Abstract: Cold air hyperventilation is an indirect challenge (cold air challenge, CACh) with high specificity and low sensitivity in defining asthmatic subjects. A small proportion of chronic obstructive pulmonary disease (COPD) patients present with positive CACh. The aim of this prospective study was to investigate the presence of factors related to cold air challenge (CACh) in COPD patients. Factors examined were FEV(1), FEV(1)/FVC, reversibility after bronchodilation, eosinophils in induced sputum, bronchial hyperresponsiveness to methacholine and the spirometric response to tiotropium compared to placebo. We studied 92 consecutive COPD patients in order to retrieve 15 CACh positive + patients. Fifteen COPD patients with negative CACh [CACh(-)], randomly selected from the initial group, were added in order to retrieve a group of 30 patients. Spearman's correlation coefficient was used in order to evaluate possible significant correlations between CACh values and study parameters. Sixteen percent of our subjects presented CACh+. CACh values were repeatable with an intraclass correlation coefficient between the two measurements 0.980 (95% CI 0.940-0.993). The only significant correlation observed was between Delta FEV(1) after CACh [Delta(C)FEV(1)] and trough FEV(1) values post tiotropium inhalation (r(2) = 0.62, p < 0.0001). When we analyzed the response to tiotropium in the 2 separate groups we found that patients with CACh+ presented significantly lower values of trough FEV(1) compared to those with CACh(-). In conclusion, a small proportion of COPD patients present with bronchial hyperresponsiveness to CACh. The only parameter related to CACh + in our study was a smaller bronchodilating effect of tiotropium.
Abstract: A patient with a known history of hypothyroidism due to Hashimoto's thyroiditis presented with a subacute, progressive sensorimotor deficit that affected the upper limbs predominantly. The electrophysiological findings progressively evolved from multifocal motor conduction block to multifocal demyelinating sensory and motor nerve involvement with conduction block, and finally to findings fulfilling the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy (CIDP). The patient did not respond adequately to intravenous immunoglobulin, whereas oral prednisone led to fast and complete recovery. This report discusses the evolution of early findings of CIDP, as well as its coexistence with Hashimoto's thyroiditis.
Abstract: BACKGROUND: Local and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements. PATIENTS & METHODS: About 45 OSA patients (mean AHI 40+/-25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-alpha and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed. RESULTS: An increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements. CONCLUSIONS: Increased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity.
Abstract: Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition.
Abstract: BACKGROUND: COPD primarily affects the lungs but also produces systemic consequences that are not reflected by the recent staging according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Body mass index (BMI) and fat-free mass index (FFMI) represent different aspects of nutrition abnormalities in COPD. We investigated whether BMI and FFMI could be related to parameters expressing airflow obstruction and limitation, exercise capacity, airway inflammation, and quality of life, and whether they would reflect the GOLD staging of the disease. METHODS: One hundred patients with clinically stable COPD equally classified into the five stages of the disease were evaluated for BMI, FFMI (measured by bioelectrical impedance analysis), airway obstruction and hyperinflation (FEV(1), FEV(1)/FVC, inspiratory capacity), exercise capacity (6-min walk distance [6MWD], Borg scale before and after 6MWD]), chronic dyspnea using the Medical Research Council (MRC) scale, airway inflammation (sputum differential cell counts, leukotriene B(4) in supernatant), and quality of life (emotional part of the chronic respiratory disease questionnaire). RESULTS: 6MWD was significantly associated with both BMI and FFMI values, while FFMI additionally presented significant correlations with MRC scale, percentage of predicted FEV(1), and FEV(1)/FVC ratio. No association was observed between the two nutritional indexes. BMI was not statistically different among patients in the five stages of COPD, while FFMI reflected the staging of the disease, presenting the highest values in stage 0. CONCLUSIONS: Nutritional status is mainly related to exercise capacity. FFMI seems to be more accurate in expressing variables of disease severity, as well as the current staging compared to BMI.
Abstract: BACKGROUND: Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.
Abstract: It is well documented that cytoplasmic Ca++ regulates sensitivity to cyclic adenosine monophosphate (cAMP). There is also evidence that Ca++ in the mucus may also modulate sensitivity to cAMP in vivo. Assuming that mucosal Ca++ could significantly change the excitability of the receptor neurons, we examined the alterations in the olfactory sensitivity by creating small changes in mucosal Ca++. Thirty one patients complaining of olfactory loss were examined and their olfactory acuity was measured before and after the administration of a sodium citrate buffer solution in the nasal cleft. Thirty patients (96.8%) improved their scores in less than an hour period of time. Furthermore, 23 of them (74.2%) realized an improvement in their own sense of smell.
Abstract: In this study, we assessed the effects of a 4 week basic military physical training programme for male recruits of the Hellenic Air Force on the number and distribution of circulating immune cells and adrenergic and adrenocortical hormonal responses. One group of recruits (exercised, n = 48) participated in moderate intermittent physical exercise, whereas a second group (non-exercised controls, n = 9) performed only light work in the barracks. Both groups participated in the same non-physical, classroom-type training and testing. Military training by the exercised group resulted in significant increases in CD4+ T-lymphocytes, renal cortisol excretion and the urinary noradrenaline/adrenaline ratio, together with reductions in neutrophils and the neutrophil/lymphocyte ratio. In the exercised group, the urinary noradrenaline/adrenaline ratio correlated positively with the training-induced changes in CD4+ T-lymphocytes and negatively with changes in the neutrophil/lymphocyte ratio. No significant relationship was found between training-induced increases in cortisol excretion and any of the peripheral blood cell alterations. Our results indicate that 4 weeks of military training consisting of intermittent moderate exercise resulted in a significant increase in CD4+ T-lymphocytes and reduction in neutrophils. These changes were probably driven by alterations in hormonal status, including the significant impact of sympathetic nervous system activation.
Abstract: STUDY OBJECTIVES: Some patients with COPD present with significant reversibility of airflow limitation after receiving bronchodilation therapy. Leukotriene B(4) (LTB(4)) has been implicated in the pathophysiology of both COPD and asthma. We tested the hypothesis that COPD patients with airflow reversibility and asthmatic patients who smoke might have similar levels of LTB(4) in exhaled breath condensate (EBC) and sputum supernatant. The repeatability and stability of LTB(4) measurements were additionally studied. DESIGN: Prospective, cross-sectional study. PATIENTS OR PARTICIPANTS: We studied 30 patients with COPD (15 smokers [FEV(1), 56% predicted; SD, 6% predicted]; 15 patients with significant reversibility in airway obstruction after bronchodilation [FEV(1), 14% predicted; SD, 2% predicted]). Fifteen asthmatic patients who smoked, with similar FEV(1) and reversibility were also studied. Ten healthy smokers served as control subjects. SETTING: A hospital research laboratory. INTERVENTIONS: Spirometry and reversibility testing were performed on the first visit. On the following day, EBC was collected for the measurement of LTB(4), and induced sputum was collected for differential cell counts and LTB(4) measurement in the sputum supernatant. MEASUREMENTS AND RESULTS: LTB(4) levels in EBC [mean (SD)] were increased in COPD patients (mean, 86.7 pg/mL; SD, 19 pg/mL) and asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL) compared to control subjects (mean, 32.3 pg/mL; SD, 10 pg/mL; p < 0.0001 for both groups). COPD patients with airflow reversibility (mean, 99.8 pg/mL; SD, 12 pg/mL) had values similar to those of asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL; p = 0.2) and higher than those of COPD patients without airflow reversibility (mean, 73.7 pg/mL; SD, 17 pg/mL; p = 0.002). Similar results were observed in the sputum supernatant. Measurements of LTB(4) in EBC and sputum were repeatable on two consecutive days, but measurements in the frozen samples of EBC and sputum were not stable after 3 weeks. CONCLUSIONS: Patients with asthma and reversible COPD presented with higher LTB(4) values compared to patients with nonreversible COPD and healthy smokers. This difference may be mainly attributed to the presence of reversibility in airway obstruction, probably as part of a common underlying inflammatory process.
Abstract: STUDY OBJECTIVE: 8-Isoprostane is considered an index of oxidative stress. Measurement of 8-isoprostane in the expired breath condensate, a totally noninvasive method, has not been used to explore the level of inflammation in pulmonary sarcoidosis. Therefore, the aim of our study was to measure the levels of 8-isoprostane in the expired breath condensate of patients with sarcoidosis, and to investigate the relation of 8-isoprostane level to disease activity. PATIENTS: We investigated 30 patients with pulmonary sarcoidosis (active disease, n = 14; nonactive disease, n = 16) and 12 healthy subjects as control group. METHODS: 8-Isoprostane was measured in the expired breath condensate of all subjects, and its levels were compared between the control and sarcoidosis groups as well as between the subgroups of patients with active and nonactive disease. In the group with sarcoidosis, 8-isoprostane levels were further correlated with markers that may reflect disease activity, such as serum angiotensin-converting enzyme (sACE) level, serum calcium level, and pulmonary function test results. RESULTS: The concentration of 8-isoprostane was increased in patients with sarcoidosis compared to control subjects (mean, 64.23 pg/mL; 95% confidence interval [CI], 37.00 to 91.46 pg/mL; vs mean, 20.75 pg/mL; 95% CI, 16.06 to 25.44 pg/mL; p = 0.04). The difference was primarily due to the patients with active disease, who had significantly higher levels of 8-isoprostane (mean, 111.4 pg/mL; 95% CI, 62.56 to 160.30 pg/mL; p < 0.001) compared to patients with nonactive disease (mean, 22.94 pg/mL; 95% CI, 15.89 to 29.99 pg/mL) or healthy subjects. 8-Isoprostane levels in patients with nonactive disease did not differ from those in healthy subjects (p > 0.05). In the patients with sarcoidosis, 8-isoprostane levels were positively correlated with sACE level (p < 0.0001, r = 0.69), but was not correlated with serum calcium level or pulmonary function test values. CONCLUSIONS: Our data suggest that 8-isoprostane levels are increased in the expired breath condensate of patients with sarcoidosis and might serve as an index of disease activity.
Abstract: OBJECTIVE: To evaluate the levels of hydrogen peroxide (H(2)O(2)) and 8-isoprostane in the expired breath condensate (EBC) of patients with COPD, and to assess the relationship between the above markers of oxidative stress and parameters expressing inflammatory process and disease severity. SETTING: Inpatient respiratory unit and outpatient clinic in tertiary care hospital. DESIGN: Cross-sectional study. PATIENTS: Thirty stable COPD patients (all smokers) with disease severity ranging from mild to severe. Ten subjects who were smokers with stage 0 disease (ie, at risk for COPD; mean [+/- SD] FEV(1), 88 +/- 5% predicted) were studied as a control group. METHODS: H(2)O(2) and 8-isoprostane levels were measured in EBC, and the values were correlated with variables expressing COPD severity (ie, FEV(1) percent predicted, dyspnea severity score (ie, Medical Research Council scale) and airway inflammation (ie, differential cell counts from induced sputum). RESULTS: The mean concentration of H(2)O(2) was significantly elevated in COPD patients compared to control subjects (mean, 0.66 micromol/L [95% confidence interval (CI), 0.54 to 0.68 micro mol/L) vs 0.31 micro mol/L [95% CI, 0.26 to 0.35 micromol/L], respectively; p < 0.0001). The difference was primarily due to the elevation of H(2)O(2) in patients with severe and moderate COPD, whose expired breath H(2)O(2) levels were significantly higher than those of patients with mild disease (mean, 0.96 micromol/L [95% CI, 0.79 to 1.13 micromol/L], 0.68 micromol/L [95% CI, 0.55 to 0.81 micromol/L], and 0.33 micromol/L [95% CI, 0.24 to 0.43 micromol/L], respectively, p < 0.0001). The mean concentration of 8-isoprostane was significantly elevated in patients with COPD compared to that of the control group (47 pg/mL [95% CI, 41 to 53 pg/mL] vs 29 pg/mL [95% CI, 25 to 33 pg/mL], respectively; p < 0.0001) but did not differ significantly among the different stages of the disease (p = 0.43). Repeatability and stability data within measurements showed that H(2)O(2) has a better repeatability and stability than 8-isoprostane. Furthermore, we observed significant correlations of H(2)O(2) with FEV(1), neutrophil count, and dyspnea score. Those correlations existed only in patients with moderate and severe disease. No correlations were found between levels of 8-isoprostane and the above parameters. CONCLUSIONS: We conclude that levels of H(2)O(2) and 8-isoprostane are elevated in the EBC of patients with COPD, but that H(2)O(2) seems to be a more repeatable and a more sensitive index of the inflammatory process and the severity of the disease.
Abstract: Inhaled prostaglandin (PG)E2 has been found to cause bronchodilation in asthmatics, although it does not have bronchodilative effects in normal subjects. The aim of this study was to investigate the levels of PGE2 in the expired breath condensate of patients with asthma, the possible contribution of smoking habit to its levels and the possible relationship between PGE2 and the degree of bronchial hyperresponsiveness, as assessed by the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20). A total of 30 mild asthmatics (15 smokers, all steroid-naive, FEV1 88+/-6 (%+/-SD)) and 20 healthy control subjects (10 smokers) were studied. Histamine challenge testing was performed in all subjects and the PD20 was determined. The results showed that asthmatic smokers had significantly higher values of PGE2 compared to asthmatic nonsmokers and control subjects (40+/-21 versus 14.5+/-4.5 versus 11.7+/-3 pg x mL(-1), respectively). Further analysis showed that PGE2 levels were significantly higher in asthmatic smokers compared to smoker and nonsmoker controls (40+/-21 versus 11.6+/-2 versus 11.7+/-4 pg x mL(-1), respectively). No significant difference was observed between asthmatic nonsmokers and both control smokers and control nonsmokers. No significant correlation was found between PGE2 levels and PD20 in all groups of asthmatics, irrespective of smoking habit. In conclusion, the elevation of prostaglandin E2 in the expired breath condensate of patients with asthma is mainly attributed to smoking habit and prostaglandin E2 levels do not predict the degree of bronchial hyperresponsiveness.
Abstract: STUDY OBJECTIVES: To determine the intracellular and extracellular Mg concentrations in patients with acute asthma and their correlation with parameters expressing the disease severity. PATIENTS: Thirty patients with acute asthma (FEV(1), 56% predicted [SD, 14.5]), 20 patients with stable asthma (FEV(1), 97% predicted [SD, 10]), and 20 healthy subjects (FEV(1), 97% predicted [SD, 8]). METHODS: Mg concentrations in erythrocytes and plasma were measured four times: at hospital admission, after 2 days, after 5 days, and at hospital discharge. Percentage of predicted FEV(1) and peak expiratory flow rate variability were recorded simultaneously. Similar measurements were carried in all study groups. RESULTS: Mg concentrations of healthy subjects and patients with stable asthma remained unchanged in both plasma and erythrocytes. Initial Mg content in erythrocytes was significantly lower in patients with acute asthma (1.77 fmmol per cell; 95% confidence interval [CI], 1.71 to 1.83) compared to normal subjects (1.94 fmmol per cell; 95% CI, 1.82 to 2.00) and patients with stable asthma (1.92 fmmol per cell; 95% CI, 1.87 to 1.96) [p < 0.0001], and it increased significantly after the resolution of the exacerbation (from 1.77 fmmol per cell [95% CI, 1.71 to 1.83] at hospital admission to 1.90 fmmol per cell [95% CI, 1.83 to 1.98] at hospital discharge; p < 0.0001). No correlation was observed between parameters of disease severity and the initial values of Mg concentrations in erythrocytes and plasma. CONCLUSIONS: Acute asthma is associated with lower erythrocyte Mg content while plasma levels remain unchanged. This decrease in intracellular Mg content occurs regardless of the severity of the exacerbation and returns to normal values after control has been achieved.
Abstract: Endogenous airway acidification, as assessed by pH in expired breath condensate, has been implicated in asthma pathophysiology. We measured pH in breath condensate of patients with inflammatory airway diseases in stable condition and examined its relationship with the inflammatory process (as assessed by differential cell counts in induced sputum), oxidative stress (as assessed by H(2)O(2) and 8-isoprostane), and nitric oxide metabolism (as assessed by total nitrate/nitrite). We studied 40 patients with bronchial asthma (20 with moderate disease, forced expiratory volume in 1 second 60 [10]% SD predicted), 20 patients with bronchiectasis, 20 patients with chronic obstructive pulmonary disease (COPD), and 10 normal subjects. Mean (95% confidence intervals) pH values were significantly lower in patients with COPD and bronchiectasis compared with patients with asthma and control subjects (7.16, 7.09-7.23 and 7.11, 7.04-7.19 versus 7.43, 7.35-7.52 and 7.57, 7.51-7.64, respectively, p < 0.0001). Patients with moderate asthma had significantly lower values compared with mild and control subjects. In patients with COPD and bronchiectasis, the values of pH were significantly correlated with both sputum neutrophilia and oxidative stress. Respectively, in patients with moderate asthma, a significant correlation was observed between pH and sputum eosinophilia, total nitrate/nitrite, and oxidative stress. The pH of the expired breath condensate might be a simple, noninvasive, inexpensive, and easily repeatable procedure for the evaluation of the inflammatory process in airway diseases.
Abstract: STUDY OBJECTIVE: To investigate which cells are the main source of hydrogen peroxide (H(2)O(2)) production in stable patients with asthma and the associations among H(2)O(2) levels, airway inflammation, and disease severity. SETTING: Inpatient respiratory unit and outpatient clinic in tertiary-care hospital. PATIENTS: Fifty stable asthmatic patients with disease severity ranging from mild to moderate. METHODS: H(2)O(2) was measured in expired breath condensate and was correlated with variables expressing both asthma severity (ie, FEV(1) percent predicted, peak expiratory flow rate [PEFR] variability, symptom score, and histamine airways responsiveness) and airway inflammation (ie, differential cell counts from induced sputum and levels of eosinophil cationic protein [ECP]). RESULTS: The mean (95% confidence interval [CI]) concentration of H(2)O(2) was significantly elevated in patients with asthma compared to that in control subjects (mean, 0.67 microM [95% CI, 0.56 to 0.77 microM] vs 0.2 microM [95% CI, 0.16 to 0.24 microM]; p < 0.0001). The difference was primarily due to the elevation of H(2)O(2) in patients with moderate asthma whose expired breath H(2)O(2) level of 0.95 microM (95% CI, 0.76 to 1.12 microM) was significantly higher from that of patients with mild-persistent and mild-intermittent asthma (mean, 0.59 microM [95% CI, 0.47 to 0.7 microM] and 0.27 [95% CI, 0.23 to 0.32 microM], respectively; p < 0.0001). H(2)O(2) concentration was positively related to sputum eosinophilia as well as to ECP concentration. A similar correlation was found between H(2)O(2) and neutrophils in patients with moderate asthma. A positive correlation was observed between H(2)O(2) level, symptom score, and PEFR variability. H(2)O(2) level was negatively related to FEV(1) percent predicted. Further analysis showed that only patients with moderate asthma who were not receiving inhaled steroids were found to have a strong relationship with the variables tested. CONCLUSIONS: Eosinophils are the predominate cells that generate H(2)O(2) in all forms of the disease, while neutrophils might be responsible for the highest levels that are observed in the more severe forms of the disease. The role of H(2)O(2) concentration in predicting the severity of the disease as well as in the inflammatory process is limited and depends on the use of inhaled steroid therapy and the classification of the severity of the disease.
Abstract: STUDY OBJECTIVES: To determine the concentration of exhaled H(2)O(2) in patients with bronchiectasis, and to study the relationship between levels of exhaled H(2)O(2), extent of disease, symptoms score, spirometry, and cellular composition obtained from induced sputum; furthermore, to account for possible confounding effects of inhaled corticosteroids (ICS) usage, long-term oral antibiotic treatment, and chronic colonization with Pseudomonas aeruginosa. DESIGN: Cross-sectional study. PATIENTS: Thirty patients with steady-state bronchiectasis. RESULTS: Mean (95% confidence interval [CI]) exhaled H(2)O(2) levels were significantly elevated in patients with bronchiectasis compared to normal subjects: 1.1 (0.87 to 1.29) microM vs 0.3 (0.19 to 0.36) microM, respectively (p < 0.0001). Patients treated with ICS had similar values as steroid-naïve patients. The group of patients with P aeruginosa colonization showed a significantly increased concentration of H(2)O(2) compared to the group without P aeruginosa colonization. Patients receiving long-term oral antibiotic treatment had significantly higher values of H(2)O(2) compared to those not receiving antibiotics. There was a significant positive correlation between H(2)O(2) and either the percentage of neutrophils in induced sputum or the extent of the disease as defined by high-resolution CT. A significant negative correlation was found between H(2)O(2) and FEV(1) percent predicted. Finally, there was a significant positive correlation between H(2)O(2) and the symptoms score. CONCLUSIONS: Patients with bronchiectasis in stable condition showed increased levels of exhaled H(2)O(2). The above-mentioned levels were not decreased either by ICS or long-term oral antibiotic treatment, but were significantly affected by chronic colonization with P aeruginosa. H(2)O(2) levels could be an indirect index of neutrophilic inflammation, impairment of lung function, and extension and severity of the disease.
Abstract: BACKGROUND: Strains of Helicobacter pylori with the cytotoxine-associated gene A (cagA) are linked to severe forms of gastroduodenal disease. Although eradication of H. pylori may predispose to the development of reflux esophagitis, the effects of CagA status on risk of esophagitis after successful H. pylori treatment are not known. METHODS: We studied 50 consecutive patients without esophagitis in whom H. pylori was eradicated successfully. CagA status was determined by immunoblotting sera from patients against H. pylori antigens. Patients underwent upper gastrointestinal endoscopy before eradication and 6, 12, 18, and 24 months after eradication or when reflux symptoms occurred. Biopsy specimens of the antrum and corpus were evaluated for gastritis before H. pylori eradication and at the end of the study. The sum of the scores for acute and chronic inflammation (both measured on a 0 [absent] to 3 [severe] scale) comprised the total gastritis severity score. RESULTS: In a multivariate proportional hazards regression analysis, positive CagA serology (hazard ratio [HR] = 10, 95% confidence interval [CI]: 1.3 to 81) and moderate-to-severe corpus gastritis (total severity score > or =4) before eradication (HR = 2.3, 95% CI: 1.2 to 6.1) were independent risk factors for the development of esophagitis after H. pylori eradication. CONCLUSION: Patients infected with strains of H. pylori that are cagA-positive are at increased risk of developing esophagitis after eradication of H. pylori.
Abstract: Production of nitric oxide (NO) is generally increased during inflammatory diseases including asthma. The eventual fate of NO is oxidation to nitrite (NO2) and nitrate (NO3), both of which are end-products of NO metabolism. Hydrogen Peroxide (H2O2) is increased in exhaled breath condensate of asthmatic subjects and may be used as a non-invasive marker of oxidative stress. NO has in some cases been shown to attenuate oxidant-induced lung injury. Total NO2/NO3 concentration and H2O2 levels were measured in expired breath condensate in 50 clinically stable asthmatics [all males, all atopics, mean age 22 (3) SD yrs, forced expiratory volume in 1 sec (FEV1) 91 (10)% predicted, PD20 to histamine 0.262 (0.16) mg 20 on inhaled steroids, 20 smokers, all steroid-naive] and in 10 normal, non-atopic subjects [all males, age 23 (4) yrs, FEV1 101 (14)% predicted, PD20 to histamine 1.3 (0.55) mg]. NO2/NO3 levels were significantly higher in patients with asthma than in normal subjects (1.08, 95% CI 0.86-1.3 microM vs. 0.6; 95% CI 0.46-0.8, P < 0.001). Patients who were on inhaled steroids had significantly ower values compared to steroid-naive (0.71, 95% CI 0.55-0.87 microM vs. 133, 95% CI 1-1.65 microM, P < 0.001). Similar results were observed between smokers and non-smokers (1.11, 95% CI 0.74-1.47 microM vs. 1.77, 95% CI 1.1-24 microM, P < 0.0001).There was a significant positive correlation between NO2/NO3 levels and H2O2 concentration in expired breath condensate (r = 0.48, P < 0.0001). No correlation was observed between NO2/NO3 levels, airway obstruction and bronchial hyper-reactivity as assessed by PD20 to histamine. Total NO2/NO3 levels in expired breath condensate are raised in patients with stable asthma and are significantly related to oxidative stress as assessed by H2O2 concentration. Measurement of expired breath NO2/NO3 and H2O2 levels may be clinically useful in the management of oxidation and inflammation mediated lung injury.
Abstract: Previous studies have assessed the protective effect of nebulized magnesium sulphate on bronchial hyperreactivity. This study investigated the effect of histamine challenge on intracellular (erythrocytes) and extracellular (plasma) levels of magnesium and the possible relationship between degree of bronchial hyperreactivity and levels of Mg in plasma and erythrocytes. The authors studied 42 mildly asthmatic patients (10 on inhaled steroids) and 20 healthy subjects. Histamine challenge was performed by the dosimeter method and provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) (FEV1) was calculated. Mg levels were measured with a calmagite colourimetric assay, both at baseline and when FEV1 had fallen by 20%. The results showed that Mg levels in plasma did not significantly change after histamine challenge (from 2.06+/-0.02 mg x dL(-1) to 2.08+/-0.02 mg x dL(-1) respectively, p=0.14). Conversely there was a statistically significant decrease in Mg levels in erythrocytes between these two time points (from 1.84+/-0.02 fmmol x cell to 1.78+/-0.02 fmmol x cell p<0.0001). Similar results were observed when the subgroups were studied separately. There was no significant correlation between PD20, the difference in both magnesium concentrations (baseline-PD20 time) or the initial values of Mg levels in erythrocytes and plasma. To conclude, histamine challenge reduces magnesium levels in erythrocytes while plasma levels remain unchanged. This histamine-induced decrease in magnesium levels occurs regardless of the diagnosis of asthma, and it is not correlated with the degree of bronchial hyperreactivity.
Abstract: BACKGROUND: Helicobacter Pylori infection has been strongly associated with upper gastrointestinal (GI) disease, especially duodenal ulcer. Endoscopy or contrast radiography is needed to diagnose and appropriately manage peptic ulcer disease. These diagnostic procedures, however, are time consuming and expensive; endoscopy is invasive and contrast radiography cannot help in the diagnosis of H pylori infection. Our aim was to examine in a prospective study the relation between serologic detection of cytotoxic associated gene (CagA) H pylori strains and endoscopic findings among young dyspeptic patients to determine whether this noninvasive test can help differentiate patients with from those without ulcers. METHODS: One hundred patients younger than 45 years with dyspepsia referred for upper GI endoscopy were included in the study. During endoscopy antral biopsy specimens were obtained for the rapid urease test and histologic examination. At histologic examination gastritis was graded from 0 (normal histologic features) to 3 (severe gastritis). After endoscopy blood was obtained for serologic determination of CagA status. RESULTS: Among the 100 patients 56 were H pylori positive and 44 were H pylori negative. In the group of 56 H pylori-positive patients 36 (64.3%) had peptic ulcers and 20 (35.7%) did not. Among patients with peptic ulcer 34 of 36 (94.4%) were CagA positive and 2 (5.6%) were CagA negative. The respective values for the group of patients without ulcers were 9 of 20 (45%) and 11 of 20 (55%). The difference in the proportion of CagA-positive subjects between the group with and that without peptic ulcer was highly significant (p < 0.0001). CONCLUSIONS: Among young patients with dyspepsia, CagA seropositivity is highly associated with duodenal ulcer at endoscopy.
Abstract: BACKGROUND: To date it is not known whether gastric juice vitamin C levels are influenced by Helicobacter pylori CagA(+) strains. The aim of the present study, therefore, was to study the impact of H. pylori CagA status on gastric juice vitamin C levels. MATERIALS AND METHODS: We studied 30 H. pylori(+) patients, and the results were compared with 10 endoscopically and histologically normal H. pylori(-) subjects (control group) who were similar to the H. pylori(+) group in terms of age and sex. In all patients, gastric juice vitamin C levels were determined and the severity of gastritis was graded on a scale of 0 (absent) to 3 (severe). CagA was determined by immunoblotting the sera from patients against H. pylori antigens. RESULTS: Among 30 H. pylori(+) patients, 20 were CagA(+) and 10 CagA(-). In the entire group of H. pylori(+) patients, the median gastric juice vitamin C levels (mg L-1) were 16.35 (range 3.5-33.6) and were significantly lower (P < 0.001) than in the control group of H. pylori(-) patients [35.5 (23.1-50.2)]. In addition, in the entire group of H. pylori(+) patients there was a highly significant (P < 0.0001) inverse correlation between the gastritis activity score and the gastric juice vitamin C levels. In the group of H. pylori CagA(+) patients, the median levels of gastric juice vitamin C were 13.8 (3.5-31.2) and were significantly lower than the corresponding levels in both the H. pylori CagA(-) group [24.8 (22-33.6), P < 0.01] and the H. pylori(-) control group [35.5 (23.1-50.2), P < 0.001], the last groups being similar. Furthermore, the gastritis activity median score in the H. pylori CagA(+) group [2 (1-3)] was significantly higher (P < 0.05) than in the H. pylori CagA(-) group [1 (1-2)]. CONCLUSION: These data indicate that infection with CagA(+) H. pylori strains significantly lowers the gastric juice vitamin C levels in comparison with CagA(-) H. pylori strains, which might have a significant impact on gastric carcinogenesis.
Abstract: H. pylori has recently been recognized as a novel risk factor of gastric cancer, but its precise role in gastric carcinogenesis is as yet unknown. The aim of the present study was to assess the relationship between H. pylori infection and vitamin C levels in gastric juice and also to examine whether eradication of H. pylori could have any impact on these levels. Gastric juice and plasma vitamin C levels were measured in 88 dyspeptic patients who had an upper gastrointestinal endoscopy. In the subgroup of H. pylori-positive patients, eradication was attempted with triple therapy. This subgroup was studied on two occasions, ie, before and after treatment. There were 58 H. pylori-positive and 30 -negative patients. Gastric juice vitamin C levels in H. pylori-positive patients were statistically lower (P < 0.001) than the levels in the H. pylori-negative patients. Triple therapy achieved eradication in 45 patients (77.6%) of the 58 H. pylori-positive patients. Before H. pylori was eradicated in these 45 patients gastric juice vitamin C levels were significantly (P < 0.001) lower than those after eradication, the latter being no different than the group of 30 H. pylori-negative patients. There was a significant (P < 0.001) improvement of gastritis after eradication, which paralleled the elevation of gastric juice vitamin C levels. No difference was noted in plasma vitamin C levels between H. pylori-negative and -positive patients or in the latter before and after H. pylori treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
