RESUMEN

Ionizing radiation is strongly linked to direct or indirect DNA damage, as with the production of reactive oxygen species (ROS), which in turn produce DNA damage products, such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In this study, we aimed to investigate the formation of 8-OHdG after irradiation in patients with non-small cell cancer (NSCLC) and its use as a biomarker. Sixteen patients with squamous and thirty-six patients with non-squamous pathology were included. An enzyme-linked-immunosorbent assay (ELISA) was performed before and after radiation. A dose-dependent relationship was confirmed: 8-OHdG plasma concentrations, increased in the total of NSCLC patients and specifically with a linear correlation in non-squamous pathology; in squamous histology, after an initial increase, a significant decrease followed after 20 Gy dose of irradiation. The pretreatment total irradiated tumor volume (cm3) was positively correlated with 8-OHdG levels in patients with squamous histology. When plotting the 8-OHdG plasma concentration at a 10 Gy irradiation dose to the baseline, the AUC was 0.873 (95% CI 0.614-0.984), p < 0.0001, with an associated criterion value of >1378 as a cutoff (sensitivity 72.7%, specificity 100%). When normalizing this ratio to BSA, the associated criterion cutoff value was >708 (sensitivity of 100%, specificity 80%). Lastly, 8-OHdG levels were closely related with the development of radiation-induced toxicities.

RESUMEN

Computational approaches could provide a viable and cost-effective alternative to expensive experiments for accurately evaluating the nonlinear constitutive behavior of cementitious nanocomposite materials. In the present study, the mechanical properties of cement paste reinforced with multi-wall carbon nanotubes (MWCNTs) are examined experimentally and numerically. A multiscale computational approach is adopted in order to verify the experimental results. For this scope, a random sequential adsorption algorithm was developed to generate non-overlapping matrix-inclusion three-dimensional (3D) representative volume elements (RVEs), considering the inclusions as straight elements. Nonlinear finite element analyses (FEA) were performed, and the homogenized elastic and inelastic mechanical properties were computed. The use of a multiscale computational approach to accurately evaluate the nonlinear constitutive behavior of cementitious materials has rarely been explored before. For this purpose, the RVEs were analyzed both in pure tension and compression. Young's modulus as well compressive and tensile strength results were compared and eventually matched the experimental values. Moreover, the effect of MWCNTs on the nonlinear stress-strain behavior of reinforced cement paste was noted. Subsequently, three-point bending tests were conducted, and the stress-strain behavior was verified with FEA in the macro scale. The numerical modeling reveals a positive correlation between the concentration of MWCNTs and improved mechanical properties, assuming ideal dispersion. However, it also highlights the impact of practical limitations, such as imperfect dispersion and potential defects, which can deteriorate the mechanical properties that are observed in the experimental results. Among the different cases studied, that with a 0.1 wt% MWCNTs/CP composite demonstrated the closest agreement between the numerical model and the experimental measurements. The numerical model achieved the best accuracy in estimating the Young's modulus (underestimation of 13%), compressive strength (overestimation of 1%), and tensile strength (underestimation of 6%) compared to other cases. Overall, these numerical findings contribute significantly to understanding the mechanical behavior of the nanocomposite material and offer valuable guidance for optimizing cement-based composites for engineering applications.

RESUMEN

It is widely known that ionizing irradiation is strongly linked to the production of reactive oxygen (ROS) and nitrative species (RNS) through which DNA damage products like 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NG) are generated, respectively. In the present study, we aimed to investigate the formation of 8-OHdG and 8-NG upon irradiation and to further explore whether alterations in their concentration levels are related to the administered radiation doses and exposure time. Our research work was conducted in blood serum samples collected from 33 breast cancer patients who received adjuvant radiotherapy. The detection of 8-OHdG and 8-NG was assessed by enzyme-linked immunosorbent assay. Our results suggest that both, 8-OHdG and 8-NG, were formed during the radiation regimen. Significant correlations with radiation dose were also demonstrated by the dose-response curves of 8-OHdG and 8-NG, fitted by logarithmic distribution and polynomial regression, respectively. More precisely, 8-OHdG and 8-NG concentrations (ng/mL) were considerably increased when patients received ionizing radiation up to 30 Gy whereas irradiation over 30 Gy did not induce any further increases. The current study supports a) the production of 8-OHdG and 8-NG during radiotherapy and b) significant correlations between either 8-OHdG or 8-NG levels and radiation doses, indicating a radiation-dose-dependent relationship.

Asunto(s)

RESUMEN

Penile squamous cell carcinoma (PeSCC) is a rare tumor and advanced PeSCC is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. We describe for the first time a case with advanced chemoradiation refractory PeSCC who had documented response to active immunotherapy with the immune checkpoint inhibitor, anti-programmed death-1 monoclonal antibody Nivolumab. The patient suffered from a poor prognosis human papillomavirus-negative PeSCC, with a somatic inactivation mutation of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in tumor cells, and treatment with Nivolumab resulted in a partial response to therapy and significant tumor shrinkage. Histology transitions and alterations in tumor-infiltrating cytotoxic CD8 T-cell lymphocytes, programmed death ligand-1 expression on tumor cells and immune cells in tumor lesion biopsies pretreatment and posttreatment with Nivolumab were observed and described. In conclusion, in patients with metastatic PeSCC active immunotherapy combinations with an anti-programmed death-1/programmed death ligand-1 agent may be beneficial and further relative clinical studies are required.

Asunto(s)

RESUMEN

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep, which leads to the presence of excessive daytime drowsiness. Regarding the psychological comorbidity in patients diagnosed with OSAS, previous studies focused mainly on depressive and secondarily on anxiety symptoms. Due to the lack of research data regarding the prevalence of anxiety and depressive symptoms as well as of alexithymic characteristics in patients with OSAS in Greece, the aim of the study was to record the above symptomatology in a sample of Greek OSAS patients and to investigate its relation to the respiratory parameter (Apnea-Hypopnea Index, AHI) of polysomnography. The study was conducted in a certified sleep laboratory. Thirty five randomly selected patients who attended the laboratory with symptoms of daytime drowsiness, fatigue, disrupted sleep and snoring, were examined for anxiety, depression and alexithymia using the Spielberger Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI) and the Toronto Alexithymia Scale (TAS-20), respectively, 24 hours prior to being submitted to polysomnography. All 35 patients met the inclusion criteria of the study (age≤75 years, no other chronic diseases and no history of major psychiatric disorders). Six patients did not meet the diagnostic criteria for OSAS and were thus used as the control group of the study. A high prevalence of anxiety (41.4%) and depressive (55.2%) symptoms and of alexithymic characteristics (41.4%) was observed in OSAS patients. Although the control group showed a higher prevalence of anxiety (66.7%) and depressive (83.3%) symptoms, there were no differences between the two groups (STAI: t=-0.927, p=0.360, BDI: t=-1.537, p=0.134, TAS-20: t=0.196, p=0.846). With regard to severity, no differences were observed between control, mild, moderate and severe OSAS subgroups (STAI: F=0.583, p=0.660, BDI: F=0.829, p=0.488, TAS-20: F=0.987, p=0.412). Females scored higher on the BDI and on the STAI compared to males (STAI: t=-2.38, p=0.039, BDI: t=-3.59, p=0.01). Finally, no correlation was observed between psychometric scores and AHI (Pearson correlation p>0.05). The study confirms the high prevalence of anxiety and depressive symptoms which has been found in previous studies. Furthermore, we found a high prevalence of alexithymic characteristics, a factor that has not been investigated previously and which is positively correlated with anxiety symptoms. The coexistence of alexithymic characteristics may further complicate the clinical manifestations of OSAS due to the fact that patients with alexithymia typically have difficulty in indentifying and describing their underlying psychological symptomatology and, moreover, tend to exhibit more, and often atypical, physical symptoms. In conclusion, the study supports the presence of a high degree of psychological burden in patients diagnosed with OSAS, regardless of the severity of their symptoms, as determined by the AHI. This comorbidity should be taken into consideration during the clinical assessment of OSAS and for the treatment planning.

Asunto(s)

RESUMEN

On 18 April 2014, a case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was laboratory confirmed in Athens, Greece in a patient returning from Jeddah, Saudi Arabia. Main symptoms upon initial presentation were protracted fever and diarrhoea, during hospitalisation he developed bilateral pneumonia and his condition worsened. During 14 days prior to onset of illness, he had extensive contact with the healthcare environment in Jeddah. Contact tracing revealed 73 contacts, no secondary cases had occurred by 22 April.

Asunto(s)

RESUMEN

Chronic Obstructive Pulmonary Disease (COPD) is mainly related to smoking habit and is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Worldwide and in Greece, COPD constitutes a major epidemiological issue. Incidence of depression and anxiety is high in the COPD population. Most studies on depression and anxiety in COPD deal with factors that are positively correlated with both of these comorbidities. The aim of our study was to assess whether two variables, sense of coherence (SOC) and perception of family support (FS), are negatively correlated with depressive and anxiety symptoms in outpatients with COPD. According to Aaron Antonovsky, sense of coherence refers to the ability of individuals to make sense of and manage events. Studies in other diseases suggest that sense of family support has a significant impact on the course and outcome of the disease, yet a limited number of reports across literature addresses the role of family support in COPD patients. In our present study one hundred twenty two (98 men and 24 women) outpatients with pure COPD were included. Age and years of education were recorded. Severity of COPD was assessed with spirometry before and after bronchodilation. All patients replied to self- administered questionnaires on depression (Beck Depression Inventory, BDI), anxiety (Spielberger State-Trait Anxiety Scale, STAI), family support (Family Support Scale, FSS-13) and sense of coherence (Sense of Coherence Scale, SOC). According to our results the mean BDI depression score was 11.65 (SD 7.35), mean trait anxiety score was 40.69 (SD 11.19), mean SOC score was 54.62 (SD 7.40) and mean FS score was 64.58 (SD 11.63). Women patients had higher anxiety scores and lower sense of family support compared to men. Significant negative correlations were evidenced between depression and sense of coherence as well as between anxiety and family support. Step-wise multiple linear regression analysis verified the results and quantified the aforementioned correlations. Notably, raising scores in sense of family support by one point reduces anxiety scores by 0.14 points, and increasing sense of coherence scores by one point reduces depression scores by 0.21 points. In sum, our study confirms the presence of high levels of anxiety and depressive symptoms in COPD patients, with females being in a more disadvantaged position as they tend to have higher levels of both. Sense of coherence and family support are both protective psychological factors against the risk of developing anxiety and depressive symptoms in these patients.

Asunto(s)

RESUMEN

The dismal prognosis of pancreatic cancer reflects into the increased recurrence rate, even after R0 pancreaticoduodenectomy. Although, conventional radiation-, chemo- or surgical therapy in much selected cases, seem to work out favorably long term, less invasive and non-toxic methods with more immediate results are always preferred, concerning the already aggravated status of this group of patients. We present hereby a comprehensive review of the literature concerning the treatment of recurrent pancreatic cancer based on the case of a patient who 20 months after a pancreaticoduodenectomy developed portal hypertension and symptomatic first degree esophageal, gastric and mesenteric varices, caused by the nearly complete splenic vein obstruction at the portal vein confluence. The varices were revascularized by a percutaneous transhepatic placement of an endovascular stent into the splenic vein, along with a sequent stereotactic body radiation therapy for the local tumor control. Thanks to the accuracy and safety of the present combined treatment, the patient one year later presents control of the disease and its complications. Our paper is the first in the international literature that tries to review all the treatment modalities available (surgical, adjuvant, neoadjuvant and palliative therapy) and their efficacy, concerning the locally recurrent pancreatic cancer; furthermore, we tried to analyze the application of the above mentioned combined therapeutic approach in similar cases, elucidating simultaneously all the questions that arise. The limited existing data in the international literature and the lack of randomized controlled trials make this effort difficult, but the physician should be aware after all of all the available and innovative treatment modalities, before he chooses one. Finally, we would like to emphasize the fact that not only the local control but also the management of the complications are important for a prolonged median survival and a better quality of life after all.

Asunto(s)

RESUMEN

BACKGROUND: Not all patients with severe chronic obstructive pulmonary disease (COPD) progressively hyperinflate during symptom limited exercise. The pattern of change in chest wall volumes (Vcw) was investigated in patients with severe COPD who progressively hyperinflate during exercise and those who do not. METHODS: Twenty patients with forced expiratory volume in 1 second (FEV(1)) 35 (2)% predicted were studied during a ramp incremental cycling test to the limit of tolerance (Wpeak). Changes in Vcw at the end of expiration (EEVcw), end of inspiration (EIVcw), and at total lung capacity (TLCVcw) were computed by optoelectronic plethysmography (OEP) during exercise and recovery. RESULTS: Two significantly different patterns of change in EEVcw were observed during exercise. Twelve patients had a progressive significant increase in EEVcw during exercise (early hyperinflators, EH) amounting to 750 (90) ml at Wpeak. In contrast, in all eight remaining patients EEVcw remained unchanged up to 66% Wpeak but increased significantly by 210 (80) ml at Wpeak (late hyperinflators, LH). Although at the limit of tolerance the increase in EEVcw was significantly greater in EH, both groups reached similar Wpeak and breathed with a tidal EIVcw that closely approached TLCVcw (EIVcw/TLCVcw 93 (1)% and 93 (3)%, respectively). EEVcw was increased by 254 (130) ml above baseline 3 minutes after exercise only in EH. CONCLUSIONS: Patients with severe COPD exhibit two patterns during exercise: early and late hyperinflation. In those who hyperinflate early, it may take several minutes before the hyperinflation is fully reversed after termination of exercise.

Asunto(s)

RESUMEN

It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with concurrent limitation of maximal exercise work rate (WRmax). A total of 20 asthmatics in a stable condition and aged 32+/-13 yrs (mean+/-SD) with a forced expiratory volume in one second (FEV1) of 101+/-21% of the predicted value were studied. Only three patients exhibited an FEV1 below the normal limits. On a first visit, patients performed a symptom-limited incremental (20 W.min(-1)) bicycle exercise test. On the second visit, the occurrence of EFL (using the negative expiratory pressure technique) and DH (via reduction in inspiratory capacity) were assessed at rest and when cycling at 33, 66 and 90% of their predetermined WRmax. FEV1 was measured to detect exercise-induced asthma, 5 and 15 min after stopping exercise at 90% WRmax. Only one patient showed EFL at rest, whereas 13 showed EFL and DH during exercise. In these 13 asthmatics, exercise capacity was significantly reduced (WRmax 75+/-9% pred) compared to the seven non-EFL patients (WRmax 95+/-13% pred). Moreover, a significant correlation of WRmax (% pred) to the change in inspiratory capacity (percentage of resting value) from rest to 90% WRmax was found. Tidal EFL during exercise was not associated with exercise-induced asthma, which was detected in only three patients. In conclusion, tidal expiratory flow limitation and dynamic hyperinflation during exercise are common in stable asthmatics with normal spirometric results and without exercise-induced asthma, and may contribute to reduction in exercise capacity.

Asunto(s)

RESUMEN

Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been studied in mechanically ventilated morbidly obese subjects. In 15 postoperative mechanically ventilated morbidly obese subjects, we assessed the prevalence of EFL [using the negative expiratory pressure (NEP) technique], PEEPi, DH, respiratory mechanics, arterial oxygenation and PEEPi inequality index as well as the levels of PEEP required to abolish EFL. In supine position at zero PEEP, 10 patients exhibited EFL with a significantly higher PEEPi and DH and a significantly lower PEEPi inequality index than found in the five non-EFL (NEFL) subjects. Impaired gas exchange was found in all cases without significant differences between the EFL and NEFL subjects. Application of 7.5 +/- 2.5 cm H2O of PEEP (range: 4-16) abolished EFL with a reduction of PEEPi and DH and an increase in FRC and the PEEPi inequality index but no significant effect on gas exchange. The present study indicates that: (a) on zero PEEP, EFL is present in most postoperative mechanically ventilated morbidly obese subjects; (b) EFL (and concurrent risk of low lung volume injury) is abolished with appropriate levels of PEEP; and (c) impaired gas exchange is common in these patients, probably mainly due to atelectasis.

Asunto(s)

RESUMEN

In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WRmax)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring. Lung function, MRC dyspnoea, HRCT score, WRmax and FL were assessed in 23 stable caucasian patients (six males) aged 56 +/- 17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WRmax was measured using a cyclo-ergometer. According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WRmax (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score. In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.

Asunto(s)

RESUMEN

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.

Asunto(s)

RESUMEN

BACKGROUND: Asthma and rhinitis often co-exist and there are data to suggest that they may be two ends of the same disease spectrum. Immunohistochemical studies have shown that eosinophilia in the airways is a feature of rhinitic patients without asthma. OBJECTIVE: The aim of our study was to examine whether cellular infiltration exists in the nasal mucosa of asthmatics even in the absence of symptoms and signs of rhinitis. METHODS: Nasal mucosa biopsies were taken from 27 non-atopic subjects and comprised nine asthmatic rhinitic patients (AR), eight asthmatic non-rhinitic patients (ANR) and 10 healthy control subjects (N). Bronchial mucosa biopsies were also taken simultaneously from some of the patients (n = 10) to determine whether there was an association between cellular infiltration in the nose and the lungs. The alkaline phosphatase-anti-alkaline phosphatase (APAAP) method was used on 6 microm thick cryostat sections using monoclonal antibodies against T cells (CD4, CD8), eosinophils (EG2) and mast cells (mast cell tryptase). Slides were counted blind and results expressed as cells per field. RESULTS: The results showed that eosinophil counts were higher in both asthma groups compared with control nasal biopsies (median values AR 8.3, ANR 9.2, N 2.1 cells per field, P < 0.01). Furthermore, there was a significant correlation between eosinophil cell counts in the nose and the airways (r = 0.851 P < 0.001). No differences in eosinophil numbers were detected between the two groups of asthmatics. Also, no differences were noted for any other cell type (i.e. CD4, CD8, tryptase) among the three study groups. CONCLUSIONS: These results show that eosinophil infiltration was present in the nasal mucosa of asthmatic patients even in the absence of rhinitis, and add further support to the hypothesis that asthma and rhinitis are clinical expressions of the same disease entity.

Asunto(s)

RESUMEN

PURPOSE: An association between activation of the renin-angiotensin system and enhanced erythropoiesis has been observed in patients with several diseases, including congestive heart failure and hypertension. Our goal was to examine whether the renin-angiotensin system is associated with secondary erythrocytosis in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Plasma renin activity, plasma aldosterone concentration, serum erythropoietin level, and serum angiotensin converting enzyme (ACE) activity were measured in 12 patients with COPD and secondary erythrocytosis [mean (+/-SD) hematocrit of 53% +/- 3%] and in 12 matched controls with COPD who did not have erythrocytosis (hematocrit 45% +/- 5%). All patients had chronic hypoxemia (PaO2 <60 mm Hg). RESULTS: Both plasma renin and aldosterone levels were threefold greater in patients with secondary erythrocytosis compared to controls. No difference in erythropoietin levels was observed between patients with or without secondary erythrocytosis. Renin levels (r = 0.45; P = 0.02) but not erythropoietin levels (r = 0.15; P = 0.47) were correlated with hematocrit in the entire sample. Renin levels and PaO2 were the only variables independently and significantly associated with hematocrit values in a multiple linear regression model. CONCLUSION: Activation of the renin-angiotensin system is associated with the development of secondary erythrocytosis in chronically hypoxemic patients with COPD. The exact mechanism is not yet fully understood, but angiotensin II may be responsible for inappropriately sustained erythropoietin secretion or direct stimulation of erythroid progenitors.

Asunto(s)

RESUMEN

Theophylline, a known phosphodiesterase inhibitor, has been widely used as an additional bronchodilator in asthmatic patients who are not adequately controlled on high-doses of inhaled steroids. However, there is growing evidence that theophylline may also have anti-inflammatory or immunomodulatory effects in asthma. This study investigated whether theophylline administration has an impact on serum levels of interleukin (IL)-4 and IL-5 in asthmatic patients. Eight asymptomatic patients aged 30+/-1.5 yrs (mean +/- SEM) with mild atopic asthma were given a single daily dose of theophylline 150 mg or placebo in an on (theophylline)-off (placebo)-on (theophylline)-off (placebo) protocol with a 3-week duration of each on- or off- interval. Determination of serum IL-4 and IL-5 was done at baseline for all subjects and on the last day of each 3-week interval for the patients under study. Serum IL-4 levels were: 35+/-6 (baseline), 19+/-3 (on-1 interval), 29.5+/-4 (off-2), 15+/-2 (on-3) and 26+/-4 pg x mL(-1) (off-4), while IL-5 levels were 27+/-5, 18+/-4, 28+/-5, 17+/-4 and 28+/-5 pg x mL(-1), respectively. Spirometry was unchanged during the study and serum theophylline levels at the end of the two on-periods were 4.5+/-0.05 and 4.2+/-0.07 microg x mL(-1), while all patients remained asymptomatic. In conclusion, the administration of a low, single, daily dose of oral theophylline in asymptomatic patients with mild atopic asthma seems to reduce circulating interleukin-4 and interleukin-5.

Asunto(s)

RESUMEN

Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.

Asunto(s)