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This paper presents a novel approach to address the challenges of self-adaptive privacy in cloud computing environments (CCE). Under the Cloud-InSPiRe project, the aim is to provide an interdisciplinary framework and a beta-version tool for self-adaptive privacy design, effectively focusing on the integration of technical measures with social needs. To address that, a pilot taxonomy that aligns technical, infrastructural, and social requirements is proposed after two supplementary surveys that have been conducted, focusing on users' privacy needs and developers' perspectives on self-adaptive privacy. Through the integration of users' social identity-based practices and developers' insights, the taxonomy aims to provide clear guidance for developers, ensuring compliance with regulatory standards and fostering a user-centric approach to self-adaptive privacy design tailored to diverse user groups, ultimately enhancing satisfaction and confidence in cloud services.
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BACKGROUND: Objective measures are required that may be used as a proxy for exacerbations in asthma. The aim was to determine the sensitivity and specificity of electronic diary data to detect severe exacerbations (SEs) of asthma. A secondary aim was to identify phenotypic variables associated with a higher risk of exacerbation. METHODS: In the BIOAIR study, 169 patients with asthma (93 severe (SA); 76 mild to moderate (MA)) recorded lung function, symptoms and medication use in electronic diaries for 1 year. Data were analysed using receiver-operator characteristics curves and related to physician-diagnosed exacerbations. Medical history and baseline clinical data were used to assess risk of exacerbation. RESULTS: Of 122 physician-diagnosed exacerbations, 104 occurred in the SA group (1.1 per patient/year), 18 in the MA group (0.2 per patient/year) and 63 were severe using American Thoracic Society/European Respiratory Society criteria. During exacerbations, peak expiratory flow (PEF) and forced expiratory volume in 1 s significantly decreased, whereas day and night symptoms significantly increased. An algorithm combining a 20% decrease in PEF or a 20% increase in day symptoms on 2 consecutive days was able to detect SEs with 65% sensitivity and 95% specificity. The strongest risk factors for SEs were low Asthma Control Questionnaire score, sputum eosinophils ≥ 3%, body mass index >25 and low quality of life (St George's Respiratory Questionnaire), with ORs between 3.61 and 2.22 (p<0.05). CONCLUSIONS: Regular electronic monitoring of PEF and asthma symptoms provides an acceptable sensitivity and specificity for the detection of SEs and may be suitable for personal internet-based monitoring of asthma control.
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Asma/diagnóstico , Budesonida/uso terapéutico , Registros Electrónicos de Salud/estadística & datos numéricos , Administración por Inhalación , Adolescente , Adulto , Anciano , Asma/tratamiento farmacológico , Asma/fisiopatología , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Budesonida/administración & dosificación , Estudios Cruzados , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Ápice del Flujo Espiratorio , Pronóstico , Estudios Prospectivos , Calidad de Vida , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1-4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. RESULTS: Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1-3 expression levels compared with non-COPD smokers (PERBB1 < 0·001; PERBB2 = 0·003; PERBB3 = 0·003) and nonsmokers (PERBB1 = 0·019; PERBB2 = 0·005; PERBB3 = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1 < 0·001). DISCUSSION: These data suggest that ERBB1-3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.
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Obstrucción de las Vías Aéreas/metabolismo , Receptores ErbB/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , ADN Complementario/biosíntesis , Volumen Espiratorio Forzado/fisiología , Humanos , Pulmón/metabolismo , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Fumar/metabolismo , Capacidad Vital/fisiologíaRESUMEN
BACKGROUND: The mechanical stress that the human diaphragm is exposed to during mechanical ventilation affects a variety of processes, including signal transduction, gene expression, and angiogenesis. OBJECTIVES: The study aim was to assess the change in the production of major angiogenic regulators [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and transforming growth factor beta 1 (TGFB1)] on the human diaphragm before and after contraction/relaxation cycles during mechanical ventilation. METHODS: This observational study investigates the diaphragmatic mRNA expression of VEGF, FGF2, and TGFB1 in surgical patients receiving general anesthesia with controlled mechanical ventilation (CMV) with muscle relaxation (group A, n = 13), CMV without muscle relaxation (group B, n = 10), and pressure support of spontaneous breathing (group C, n = 9). Diaphragmatic samples were obtained from each patient at two time points: 30 min after the induction of anesthesia (t1) and 90 min after the first specimen collection (t2). RESULTS: No significant changes in the mRNA expression of VEGF, FGF2, and TGFB1 were documented in groups A and C between time points t1 and t2. In contrast, in group B, the mRNA levels of the above angiogenic factors were increased in time point t2 compared to t1, a finding which was statistically significant (pVEGF = 0.003, pFGF2 = 0.028, pTGFB1 = 0.001). CONCLUSIONS: These findings suggest that the molecular response of the human diaphragm before and after application of diverse modes of mechanical ventilation is different. Angiogenesis via the expression of VEGF, FGF2, and TGFB1 was only promoted in CMV without muscle relaxation, and this may have important clinical implications.
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Diafragma/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Respiración Artificial , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anestesia General , Femenino , Humanos , Persona de Mediana Edad , Relajación Muscular , Neovascularización FisiológicaRESUMEN
Purpose: To estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus. Patients and Methods: This was a population-based, random-digit dialing, telephone nation-wide survey to recruit patients with asthma. Among 8996 random landline-telephone contacted from the five major urban and rural regions of Cyprus, 1914 were finally met the age criterion of ≥18 years old and 572 completed valid screening for prevalence estimation. The participants filled a short screening questionnaire in order for asthma cases to be recognized. Then, asthma cases filled the main ECRHS II questionnaire and were evaluated by a pulmonary physician. All underwent spirometry. Data on demographic characteristics, educational level, profession, smoking status, Body Mass Index (BMI), Total IgE and Eosinophil Cationic Protein levels were measured. Results: The overall prevalence of bronchial asthma in adults in Cyprus was 5.57% (61.1% men and 38.9% women). Among the participants with self-reported bronchial asthma 36.1% were current smokers, while 12.3% were obese (BMI >30). A total value of IgE >115 IU and Eosinophil Cationic Protein (ECP) >20 IU was found in 40% of the participants with established bronchial asthma. Wheezing and chest tightness were the most frequently reported symptoms in asthma patients (36.1% and 34.5%, respectively), while 36.5% experienced at least one exacerbation during the last year. Interestingly, most of the patients were under-treated (14.2% were on maintenance asthma treatment, and 18% used solely reliever medication). Conclusion: This was the first study estimating asthma prevalence in Cyprus. Asthma affects almost 6% of the adult population, with higher prevalence in urban areas and in men compared to women. Interestingly, one-third of the patients were uncontrolled and under-treated. This study revealed that in Cyprus there is space for improvement in the management of asthma.
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BACKGROUND: Omalizumab is a recombinant humanized anti-IgE monoclonal antibody indicated as an add-on treatment for severe allergic asthma, inadequately controlled despite high dose of inhaled corticosteroids (ICS) and long-acting b2-agonists. OBJECTIVES: Medical registries were used to evaluate the 4 months, 1 and 4 years effectiveness of omalizumab treatment, in a non-interventional, observational "real-life" study. METHODS: Sixty patients with severe persistent allergic asthma from 5 South-Eastern Mediterranean centres from Crete and Cyprus were evaluated. Effectiveness outcomes included spirometry, severe asthma exacerbations rate, level of asthma control (ACT), and additional asthma medication (inhaled steroids). RESULTS: Outcome variables improved after 4 months and sustained after 1 and 4 years treatment with Omalizumab. FEV1 improved statistically significant at all time points versus baseline [ΔFEV1 (% pred.) = +21 p = 0.008 at 4 months, ΔFEV1 (% pred.) = +24.5 p < 0.0001 at 4 years after treatment]. Similarly, FVC increased statistically significant versus baseline [ΔFVC (% pred.) = +20 p = 0.002 at 4 months, ΔFVC (% pred.) = +22.6 p = 0.0002 at 4 years]. The level of asthma control as evaluated by ACT was significantly improved after treatment (+12% p = 0.001 at 4 months, +24% p < 0.0001 at 4 years). Omalizumab treatment reduced significantly asthma exacerbations rate (-65% p = 0.0002 at 1 year, and -70% p < 0.0001 at 4 years). The use of inhaled steroids decreased statistically significant after 4 months (p = 0.017), 1 year (p = 0.029) and 4 years (p = 0.014) of omalizumab treatment. CONCLUSIONS: This long-term "real-life" study demonstrated significant improvement in lung function and other clinical outcomes after omalizumab treatment, evident at 4 months, and sustained after 1 and 4 years suggesting its efficacy in severe allergic asthma, in the "real-life" practice.
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Antiasmáticos/uso terapéutico , Anticuerpos Antiidiotipos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Anciano , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Anticuerpos Antiidiotipos/administración & dosificación , Anticuerpos Antiidiotipos/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Asma/complicaciones , Asma/etiología , Estudios de Cohortes , Recolección de Datos , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado , Humanos , Hipersensibilidad/complicaciones , Cuidados a Largo Plazo , Masculino , Región Mediterránea , Persona de Mediana Edad , Omalizumab , Espirometría , Resultado del Tratamiento , Capacidad VitalRESUMEN
BACKGROUND-AIM: C-reactive protein (CRP) is directly implicated in atherogenesis and associated cardiovascular morbidity in patients with obstructive sleep apnea (OSA). Effective continuous positive airway pressure (CPAP) treatment has been shown to gradually decrease CRP levels and thus consequently improve disease-related cardiovascular morbidity. However, the influence of gender on the CRP evolution pattern has never been assessed before. The aim of our study was to investigate possible gender differences in CRP evolution in OSA patients 3 and 6 months after the start of effective CPAP treatment. METHODS: The study population consisted of 436 patients (252 males/184 females) with newly diagnosed moderate to severe OSA and good CPAP compliance assessed by a thorough follow up. High-sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and at the third and sixth month of the follow-up period. RESULTS: C-reactive protein values showed a statistically significant decrease at the third and sixth month of CPAP therapy [initial values 0.79 ± 0.65 mg/dL versus 0.70 ± 0.52 mg/dL (p < 0.05) after 3 months and 0.30 ± 0.33 mg/dL (p < 0.001) after 6 months of CPAP therapy]. When patients were divided into males and females, the above evolution pattern was changed. At the third month time point, the CRP values showed a statistically significant decrease only in males (from 0.74 ± 0.53 mg/dL to 0.61 ± 0.5 mg/dL, p < 0.01) while females showed only minimal and insignificant changes (from 0.87 ± 0.79 mg/dL to 0.83 ± 0.51 mg/dL, p > 0.05). After 6 months' treatment, CRP decreased significantly in both genders (males from 0.74 ± 0.53 mg/dL to 0.28 ± 0.32 mg/dL, p < 0.001 and females from 0.87 ± 0.79 mg/dL to 0.34 ± 0.36 mg/dL, p < 0.001). CONCLUSION: Our results suggest a delay in the normalization of CRP levels in females despite effective CPAP treatment. A time period of at least 6 months appeared to be required in women in order to reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP's protective role in males is achieved at an earlier time point. Gender-related hormonal and genetic factors may influence the above CRP evolution pattern.
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Proteína C-Reactiva/metabolismo , Presión de las Vías Aéreas Positiva Contínua , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Apnea Obstructiva del Sueño/terapia , Adulto , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Femenino , Estudios de Seguimiento , Grecia , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/epidemiologíaRESUMEN
According to the American Thorasic Society (ATS)/European Respiratory Society (ERS) Statement, chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with a strong genetic component, characterized by airflow limitation that is not fully reversible, but is usually progressive and associated with an enhanced inflammatory response of the lung to noxious particles or gases. The main features of COPD are chronic inflammation of the airways and progressive destruction of lung parenchyma and alveolar structure. The pathogenesis of COPD is complex due to the interactions of several mechanisms, such as inflammation, proteolytic/antiproteolytic imbalance, oxidative stress, DNA damage, apoptosis, enhanced senescence of the structural cells and defective repair processes. This review focuses on the effects of oxidative DNA damage and the consequent immune responses in COPD. In susceptible individuals, cigarette smoke injures the airway epithelium generating the release of endogenous intracellular molecules or danger-associated molecular patterns from stressed or dying cells. These signals are captured by antigen presenting cells and are transferred to the lymphoid tissue, generating an adaptive immune response and enhancing chronic inflammation.
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Daño del ADN/fisiología , Estrés Oxidativo/fisiología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Animales , Reparación del ADN/fisiología , Inestabilidad Genómica , Humanos , Repeticiones de Microsatélite/genética , MutaciónRESUMEN
BACKGROUND: There have been reports that optimal CPAP pressure can be predicted from a previously derived formula, with the Hoffstein formula being the most accurate and accepted in the literature so far. However, the validation of this predictive model has not been applied in different clinical settings. Our aim was to compare both the Hoffstein prediction formula and a newly derived formula to the CPAP pressure setting assessed during a formal CPAP titration study. METHODS: We prospectively studied 1,111 patients (871 males/240 females) with obstructive sleep apnea hypopnea syndrome (OSAHS) undergoing a CPAP titration procedure. In this large population sample, we tested the Hoffstein formula, utilizing body mass index (BMI), neck circumference and apnea/hypopnea index (AHI), and we compared it with our new formula that included not only AHI and BMI but also smoking history and gender adjustment. RESULTS: We found that using the Hoffstein prediction formula, successful prediction (predicted CPAP pressure within ±2 cm H(2)O compared to the finally assessed optimum CPAP pressure during titration) was accomplished in 873 patients (79%), with significant correlation between CPAP predicted pressure (CPAPpred(1)) and the optimum CPAP pressure (CPAPopt) [r = 0.364, p < 0.001]. With the new formula, including smoking history and gender adjustment, successful prediction was accomplished in 1,057 patients (95%), with significant correlation between CPAP predicted pressure (CPAPpred(2)) and the CPAPopt (r = 0.392, p < 0.001). However, there was a highly significant correlation between the two formulas (r = 0.918, p < 0.001). CONCLUSIONS: We conclude that the level of CPAP necessary to abolish sleep apnea can be successfully predicted from both equations, using common clinical measurements and prediction formulas that may be useful in calculating the starting pressure for initiating CPAP titration. It may also be possible to shorten CPAP titration and perhaps in selected cases to combine it with the initial diagnostic study.
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Algoritmos , Presión de las Vías Aéreas Positiva Contínua/normas , Comparación Transcultural , Apnea Obstructiva del Sueño/terapia , Adulto , Anciano , Presión del Aire , Femenino , Grecia , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/diagnóstico , Estadística como AsuntoRESUMEN
Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients' isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.
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BACKGROUND: C-reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1-year follow-up period in obstructive sleep apnoea (OSA) patients under CPAP treatment. METHODS: Five hundred and twenty-eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow-up period. Patients were divided into good and poor CPAP compliance groups. RESULTS: A significant reduction in CRP levels was observed after CPAP therapy (0·74±0·62mgdL(-1) vs. 0·31±0·29mgdL(-1) , P<0·001) in the whole patient group. The evolution of CRP values showed a gradual decrease at 3months with a steep decline at 6months, reaching a plateau after this time point. When the patients were divided into those with good and poor compliance with CPAP therapy, the above CRP evolution pattern was observed only in the former group. CONCLUSION: Good CPAP compliance results in a significant CRP reduction. To achieve the best positive impact on cardiovascular morbidity and mortality, a time period of at least 6months of CPAP use is required.
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Proteína C-Reactiva/metabolismo , Presión de las Vías Aéreas Positiva Contínua/métodos , Apnea Obstructiva del Sueño/terapia , Adulto , Proteína C-Reactiva/análisis , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Apnea Obstructiva del Sueño/fisiopatología , Estadística como Asunto , Factores de Tiempo , Resultado del TratamientoRESUMEN
Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited. p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control. Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals. Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups. Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups. On the other hand, bcl2 expression did not differ between the two groups in all three cell types. The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients. Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD.
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Apoptosis , Pulmón/química , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Proteína p53 Supresora de Tumor/análisis , Anciano , Células Epiteliales Alveolares/química , Células Epiteliales Alveolares/patología , Western Blotting , Estudios de Casos y Controles , Humanos , Inmunohistoquímica , Pulmón/patología , Linfocitos/química , Linfocitos/patología , Macrófagos Alveolares/química , Macrófagos Alveolares/patología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/patología , Transducción de Señal , Fumar , Regulación hacia ArribaRESUMEN
BACKGROUND: Instability of the Microsatellite DNA Instability (MSI) and Loss of Heterozygosity (LOH) have been previously detected in sputum cells of COPD patients. However, the particular cell subpopulation exhibiting genetic instability in COPD was uncertain. The aim of this study was to determine which cell type expresses Microsatellite DNA Instability in sputum and BALF samples from COPD patients. METHODS: Thirty-five COPD patients and 30 non-COPD smokers were studied. Sputum was induced from 20 COPD patients and 20 non-COPD smokers and BALF was obtained from 15 COPD patients and 10 non-COPD smokers. The sputum cell pellet and BALF samples were processed using immunomagnetic technology to separate antibody-specific cell subpopulations, using CD45+ for leukocytes, Epithelial enrich (MACS) for sputum epithelial cells and HEA-human epithelial antigen-(Dynal) for BAL epithelial cells. Microsatellite DNA amplification was performed using specific primers, namely G29802, D6S2223, D6S344, D6S263, D5S207, D13S71, RH70958, and D17S250. The presence of MSI and/or LOH was analyzed with LI-COR Saga GT Microsatellite Analysis Software. MEASUREMENTS AND MAIN RESULTS: None of the non-COPD smokers exhibited any genetic alteration. MSI and LOH were found in 15 cases (8 MSI and 7 LOH) in sputum and BAL samples. MSI and/or LOH were revealed only in the epithelial barrier cells. LOH was detected in D5S207, D6S344, G29802 and D17S250 microsatellite markers, while MSI in D13S71, D5S207 and D6S344. The entire leukocyte subpopulation exhibited no genetic alteration. CONCLUSIONS: Our results support the hypothesis that chronic inflammation and oxidative burden in COPD can lead to DNA damage of the lung epithelial barrier cells, detected at the Microsatellite DNA level. Further studies are required to investigate the significance of these findings in the pathogenesis of COPD.
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Daño del ADN , Células Epiteliales/metabolismo , Pulmón/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Fumar , Anciano , Líquido del Lavado Bronquioalveolar/inmunología , Femenino , Humanos , Pérdida de Heterocigocidad , Pulmón/inmunología , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Pruebas de Función Respiratoria , Esputo/inmunologíaRESUMEN
The prevalence of laryngopharyngeal reflux (LPR) has been constantly rising in the western world and affects today an alarmingly high percentage of the general population. Even though LPR and gastroesophageal reflux disease (GERD) are both the product of gastroesophageal reflux and seem to be sibling disorders, they constitute largely different pathological entities. While GERD has been for a long time identified as a source of esophageal disease, LPR has only recently been associated with head and neck disorders. Despite the high incidence of LPR and its great impact on patients' quality of life, little is known regarding its pathogenesis. On the other hand, studying the molecular and genetic basis of a disease is of fundamental importance in medicine as it offers better insight into the pathogenesis and opens new, disease-specific therapeutic trends. The aim of this study is to enlighten any known or suspected molecular mechanisms that contribute to the pathogenesis of LPR, and to suggest new trends for future research.
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Reflujo Gastroesofágico/genética , Reflujo Gastroesofágico/patología , Enfermedades de la Laringe/genética , Enfermedades de la Laringe/patología , Enfermedades Faríngeas/genética , Enfermedades Faríngeas/patología , Biopsia , Monitorización del pH Esofágico , Esófago/fisiopatología , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/fisiopatología , Expresión Génica , Humanos , Mucosa Intestinal/patología , Enfermedades de la Laringe/complicaciones , Enfermedades de la Laringe/fisiopatología , Laringoscopía , Enfermedades Faríngeas/complicaciones , Enfermedades Faríngeas/fisiopatología , Calidad de VidaRESUMEN
Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.
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Chronic Obstructive Pulmonary Disease is characterized by an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking. Although COPD affects the lung, it also produces significant systemic consequences. Inflammation, proteases-antiproteases imbalance, oxidative stress, tissue damage and tissue repair, apoptosis and several genes seem to be involved in the pathogenesis of the disease. The cellular and molecular events underlying COPD pathogenesis are driven by multifunctional molecules including enzymes, cytokines, chemokines, growth factors, lipid mediators and their respective receptors. A large number of biomarkers evaluated in COPD, showed a high degree of redundancy. Nevertheless, current understanding of the pathobiology of COPD suggests a number of biomarkers as potential candidates. The development of relevant markers of lung damage, pulmonary inflammation, and systemic disease will be essential to our further understanding of the natural history of COPD and the discovery of new, effective treatments for its progression. This review summarizes recent findings, on potential pulmonary biomarkers in the induced sputum, the exhaled air condensate, the peripheral blood, the urine, the bronchoalveolar lavage fluid, and in selective cases, in bronchial biopsies.
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Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Biomarcadores/metabolismo , Pruebas Respiratorias , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Pruebas Hematológicas , Humanos , Esputo/química , Esputo/citología , UrinálisisRESUMEN
The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity. C-erbB-1 was overexpressed in older patients, in squamous-cell carcinomas and in poorly-differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and significantly correlated with female gender, while the c-erbB-1/2 pair with older age. Response to chemotherapy was significantly reduced in patients with tumours overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4 receptor pairs. Patients' overall survival was significantly correlated with the co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest that specific receptors overexpression or co-overexpression is correlated with patients' disease control rate and outcome. A better understanding of the overexpression of the heterodimerized partners of c-erbB family receptors may provide a useful predictive indicator of response to molecular targeted therapies with c-erbB inhibitors.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas/metabolismo , Receptor ErbB-2/análisis , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Genetic alterations in the microsatellite DNA level have been successfully detected in sputum samples of patients with COPD and have been shown to be disease specific. Furthermore, previous studies have shown that inflammation coexists in the nasal mucosa of patients with COPD. The aim of this study was to assess the presence of MSI in nasal cytological samples of patients with COPD comparing the results with sputum samples of the same individuals. Nasal brush samples, sputum samples obtained by induction, and peripheral blood from 20 patients with COPD were analyzed. DNA was extracted and analyzed for MSI using the following microsatellite markers: RH70958, D5S207, D6S344, D6S263, G29802, D13S71, D14S588, D14S292 and D17S250. Microsatellite analysis was also performed in 8 healthy non-smokers. MSI was detected in the sputum samples of 7 patients with COPD (35%). In contrast, no microsatellite DNA instability was noted in the nasal cytological samples of the same COPD patients. In addition, no genetic alteration was detected in the control group. These results suggest that MSI is a specific finding for the target organ of COPD, i.e. the lungs, despite the fact that inflammation coexists in the nasal mucosa of COPD patients. Our study supports the hypothesis that MSI could be an index of the somatic-acquired genetic alterations in the lungs of COPD patients.