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Pulmonary tuberculosis caused by Mycobacterium caprae was diagnosed in a 65-year-old goat breeder from northern Greece. This case represents a documented occupational transmission of M. caprae and highlights the importance of enhanced laboratory screening and increased surveillance for zoonotic tuberculosis control.
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Mycobacterium bovis , Mycobacterium tuberculosis , Exposición Profesional , Tuberculosis , Anciano , Agricultores , Grecia , Humanos , MasculinoRESUMEN
Severe Mycolicibacter kumamotonensis-pulmonary disease was diagnosed in a 68-year-old immunocompetent woman in Greece; the disease was initially treated as tuberculosis. The patient responded favorably to a new treatment regimen of azithromycin, amikacin, moxifloxacin, and linezolid. Complete symptom resolution and radiologic improvement resulted.
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Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Anciano , Antibacterianos , Femenino , Grecia , Humanos , Mycobacteriaceae , Micobacterias no TuberculosasRESUMEN
This study aimed to evaluate the pharmacokinetic profile of moxifloxacin (MXF) in serum and sputum/bronchial secretions of 22 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the ward and intensive care unit (ICU). The data showed that ICU patients had lower concentrations in secretions (P = 0.01). However, no other statistically significant differences were observed in pharmacokinetic parameters and penetration in secretions between ward and ICU patients. MXF showed a favorable pharmacokinetic profile, and the pharmacodynamic targets for common pathogens for AECOPD were achieved.
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Antibacterianos/farmacología , Infecciones Bacterianas/prevención & control , Moxifloxacino/farmacocinética , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Anciano , Cuidados Críticos , Progresión de la Enfermedad , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Moxifloxacino/uso terapéutico , Estudios ProspectivosRESUMEN
Therapeutic drug monitoring (TDM) of moxifloxacin is recommended to improve the response to tuberculosis treatment and reduce acquired drug resistance. Limited sampling strategies (LSSs) are able to reduce the burden of TDM by using a small number of appropriately timed samples to estimate the parameter of interest, the area under the concentration-time curve. This study aimed to develop LSSs for moxifloxacin alone (MFX) and together with rifampin (MFX+RIF) in tuberculosis (TB) patients. Population pharmacokinetic (popPK) models were developed for MFX (n = 77) and MFX+RIF (n = 24). In addition, LSSs using Bayesian approach and multiple linear regression were developed. Jackknife analysis was used for internal validation of the popPK models and multiple linear regression LSSs. Clinically feasible LSSs (one to three samples, 6-h timespan postdose, and 1-h interval) were tested. Moxifloxacin exposure was slightly underestimated in the one-compartment models of MFX (mean -5.1%, standard error [SE] 0.8%) and MFX+RIF (mean -10%, SE 2.5%). The Bayesian LSSs for MFX and MFX+RIF (both 0 and 6 h) slightly underestimated drug exposure (MFX mean -4.8%, SE 1.3%; MFX+RIF mean -5.5%, SE 3.1%). The multiple linear regression LSS for MFX (0 and 4 h) and MFX+RIF (1 and 6 h), showed mean overestimations of 0.2% (SE 1.3%) and 0.9% (SE 2.1%), respectively. LSSs were successfully developed using the Bayesian approach (MFX and MFX+RIF; 0 and 6 h) and multiple linear regression (MFX, 0 and 4 h; MFX+RIF, 1 and 6 h). These LSSs can be implemented in clinical practice to facilitate TDM of moxifloxacin in TB patients.
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Antituberculosos/farmacocinética , Monitoreo de Drogas/métodos , Moxifloxacino/farmacocinética , Tuberculosis/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Área Bajo la Curva , Teorema de Bayes , Monitoreo de Drogas/estadística & datos numéricos , Quimioterapia Combinada , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Moxifloxacino/uso terapéutico , Reproducibilidad de los Resultados , Rifampin/uso terapéuticoRESUMEN
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30â days, 81.1% and 56.7%, respectively at 60â days; 85.5% and 80.5%, respectively at 90â days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.
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Antituberculosos/uso terapéutico , Diarilquinolinas/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Carbapenémicos/uso terapéutico , Clofazimina/uso terapéutico , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Humanos , Linezolid/uso terapéutico , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Retrospectivos , Esputo/metabolismo , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.
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Antibacterianos/farmacocinética , Líquidos Corporales/metabolismo , Fluoroquinolonas/farmacocinética , Derrame Pleural/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/análisis , Antibacterianos/uso terapéutico , Líquidos Corporales/química , Femenino , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/análisis , Fluoroquinolonas/uso terapéutico , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Moxifloxacino , Cavidad Pleural/química , Cavidad Pleural/metabolismo , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Natural killer (NK) cells appear to be involved in the development of interstitial lung diseases (ILD). The purpose of this study was to investigate the involvement of NK and natural killer T (NKT)-like cells in two recognized cytotoxic ILD with systemic character, hypersensitivity pneumonitis (HP) and cryptogenic organizing pneumonia (COP), compared with idiopathic pulmonary fibrosis (IPF) and controls. METHODS: Bronchoalveolar lavage fluid (BALF) and peripheral blood (PBL) cells and lymphocyte subsets of 83 patients (26 with COP, 19 with HP and 38 with IPF) and 10 controls were prospectively studied by flow cytometry. RESULTS: The percentage of NK and NKT-like cells was lower in BALF than in PBL in all patient groups and controls. Patients with COP presented with statistically significantly higher NK and NKT-like cell counts in BALF compared with controls (P = 0.044 and P = 0.05 respectively) and IPF (P = 0.049 and P = 0.045 respectively). BALF NKT-like cell count correlated with PBL NKT-like cell count only in COP (r = 0.627, P = 0.002). In addition, a significant positive correlation between BALF NKT-like cell and PBL cytotoxic T CD8+ cell count was observed in COP (r = 0.562, P = 0.006) but not in HP, IPF or controls. CONCLUSIONS: Our study provides for the first time evidence for the implication of NKT-like cells in the pathogenesis of COP, as part of both localized and systemic cytotoxicity.
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Células Sanguíneas/patología , Líquido del Lavado Bronquioalveolar/citología , Neumonía en Organización Criptogénica/patología , Células Asesinas Naturales/patología , Células T Asesinas Naturales/patología , Anciano , Alveolitis Alérgica Extrínseca/patología , Linfocitos T CD8-positivos/patología , Estudios de Casos y Controles , Recuento de Células , Femenino , Humanos , Fibrosis Pulmonar Idiopática/patología , Pulmón/patología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The COPD assessment test (CAT) is a short questionnaire designed to assess the impairment in health status of COPD patients. We aimed to determine the change of the CAT in COPD patients after 1 year of treatment and test the association between the score and clinical and lung function variables. Methods A cohort of 111 newly diagnosed COPD patients in primary care was evaluated at baseline and one year after the implementation of the recommended treatment according to the Global Initiative for the management of COPD (GOLD). Results Most of the patients (82%) were diagnosed with mild to moderate airflow limitation (mean FEV1 72 ± 21.5% predicted) and the CAT score increased in proportion with the GOLD stage of severity. The CAT significantly correlated with the number of exacerbations, visits to general practitioners and days of hospitalization both at the beginning and at 1 year follow-up. A strong negative correlation between the CAT score and FEV1 predicted was also observed. The CAT was responsive to the application of treatment with a significant improvement in the mean score (95% confidence interval) following 12 months of treatment by -2.4 (-2.9, -1.9) despite the small decline in lung function indices. The number of exacerbations in the preceding year and FEV1 were independent predictors of the CAT score in the general linear model. Conclusion The CAT questionnaire may serve as a simple, measurable tool complementary to spirometry in the assessment of severity and of response to treatment in unselected COPD patients in primary care.
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Servicios de Salud/estadística & datos numéricos , Estado de Salud , Hospitalización , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: Tracheostomy is commonly used in intensive care unit (ICU) patients who are expected to be on long-term mechanical ventilation or suffer from emergency upper airway obstruction. However, some studies have conflicting findings regarding the optimal technique and its timing and benefits. AIM: To provide evidence of practice, characteristics, and outcome concerning tracheostomy in an ICU of a tertiary care hospital. METHODS: This was a retrospective cohort study including adult critical care patients in a single ICU for two consecutive years. Patients' demographic characteristics, severity of illness (APACHE II score), level of consciousness [Glasgow Coma Scale (GCS)], comorbidities, timing and type of tracheostomy procedure performed and outcome were recorded. We defined late as tracheostomy placement after 8 days or no tracheotomy. RESULTS: Data of 660 patients were analyzed (median age of 60 years), median APACHE II score of 19 and median GCS score of 12 at admission. Tracheostomy was performed in 115 patients, of whom 63 had early and 52 late procedures. Early tracheostomy was mainly executed in case of altered level of consciousness and severe critical illness polyneuromyopathy, however there were no significant statistical results (47.6% vs 36.5%, P = 0.23) and (23.8% vs 19.2%, P = 0.55) respectively. Regarding the method selected, early surgical tracheostomy (ST) was conducted in patients with maxillofacial injuries (50.0% vs 0.0%, P = 0.033), whereas late surgical tracheostomy was selected for patients with goiter (44.4% vs 0.0% P = 0.033). Patients with early tracheostomy spent significantly fewer days on mechanical ventilation (15.3 ± 8.5 vs 22.8 ± 9.6, P < 0.001) and in ICU in general (18.8 ± 9.1 vs 25.4 ± 11.5, P < 0.001). Percutaneous dilatation tracheostomy (PDT) vs ST was preferable in older critical care patients in the case of Central Nervous System underlying cause of admission (62.5% vs 26.3%, P = 0.004). ST was the method of choice in compromised airway (31.6%, vs 7.3% P = 0.008). A large proportion of patients (88/115) with tracheostomy managed to wean from mechanical ventilation and were transferred out of the ICU (100% vs 17.4%, P < 0.001). CONCLUSION: PDT was performed more frequently in our cohort. This technique did not affect mechanical ventilation days, ventilator-associated pneumonia (VAP), ICU length of stay, or survival. No complications were observed in the percutaneous or surgical tracheostomy groups. Patients undergoing early tracheostomy benefited in terms of mechanical ventilation days and ICU length of stay but not of discharge status, presence of VAP, or survival.
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Mycobacterium abscessus is a difficult-to-treat, multidrug-resistant human pathogen. Relebactam has been shown to inhibit M. abscessus ß-lactamase (BLAMab) and increase the activity of imipenem and amoxicillin. We present two cases of lung infection due to M. abscessus, one caused by M. abscessussubsp. massiliense and the other by subsp. abscessus. Both strains showed moderate sensitivity to imipenem, and the second strain was also resistant to macrolides. A multidrug antibiotic regimen was administered in both cases, which included imipenem/cilastatin/relebactam adjusted to the estimated glomerular filtration rate (eGFR) and amoxicillin for three months. The regimen was well tolerated and both patients improved both clinically and radiologically after the first phase of treatment. The results of our patients indicate that the combination of imipenem/cilastatin/relebactam and amoxicillin could be used in the future in difficult infections by M. abscessus.
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Elexacator/tezacaftor/ivacaftor (ETI) has improved cystic fibrosis (CF) outcomes. A reduction in use of maintenance medication after its initiation has been reported. Seventy-one adult people with CF (PwCF) who are followed in three CF centers and completed one year of treatment with ETI were included in this study. Their use of inhaled dornase-α, colistin, tobramycin, aztreonam and levofloxacin during this period was compared with the corresponding use during one year without ETI, using the Medication Possession Ratio (MPR). MPR was significantly decreased after ETI initiation for dornase-α (67±35% vs 48±40%, p<0.001) and for all four inhaled antibiotics together (62±33% vs 41±37%, p<0.001). The findings of this multi-center, retrospective, study suggest that the initiation of ETI significantly leads to decrease in use of standard inhaled medication in PwCF. The significance of this finding in the course of the disease is yet to be investigated by larger prospective clinical trials.
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Fibrosis Quística , Indoles , Pirazoles , Piridinas , Pirrolidinas , Quinolonas , Adulto , Humanos , Fibrosis Quística/diagnóstico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Estudios Prospectivos , Estudios Retrospectivos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Mutación , Benzodioxoles/efectos adversos , Aminofenoles/efectos adversosRESUMEN
Rifampicin is a widely used anti-tuberculosis agent. Apart from hepatotoxicity, rifampicin can rarely lead to adverse reactions of immunologic nature such as acute renal failure (ARF). We report the case of 57-year-old previously healthy man under treatment for pulmonary tuberculosis who presented with hemolysis and severe ARF. Rifampicin was discontinued and the patient was treated with fluid repletion, iv furosemide and dialysis therapy. Kidney biopsy revealed acute tubulointerstitial nephritis with no evidence of granulomas. The patient significantly improved and was discharged after 51 days of hospitalization. Clinicians using rifampicin should be aware of this rather uncommon but severe complication.
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Lesión Renal Aguda/inducido químicamente , Antibióticos Antituberculosos/efectos adversos , Hemólisis , Rifampin/efectos adversos , Tuberculosis Pulmonar/tratamiento farmacológico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: We aimed to evaluate the pharmacokinetic profile of tigecycline in plasma and its penetration to sputum in moderately ill patients with an infectious acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: Eleven patients hospitalized with acute respiratory failure due to an acute COPD exacerbation with clinical evidence of an infectious cause received tigecycline 50 mg twice daily after an initial loading dose of 100 mg. Blood and sputum samples were collected at steady state after dose seven. RESULTS: In plasma, mean Cmax pl was 975.95 ± 490.36 ng/mL and mean Cmin pl was 214.48 ±140.62 ng/mL. In sputum, mean Cmax sp was 641.91 ± 253.07 ng/mL and mean Cmin sp was 308.06 ± 61.7 ng/mL. In plasma, mean AUC 0-12 pl was 3765.89 ± 1862.23 ng*h/mL, while in sputum mean AUC 0-12 sp was 4023.27 ± 793.37 ng*h/mL. The mean penetration ratio for the 10/11 patients was 1.65 ± 1.35. The mean Free AUC0-24 pl/MIC ratio for Streptococcus pneumoniae and Haemophilus influenzae was 25.10 ± 12.42 and 6.02 ± 2.97, respectively. CONCLUSIONS: Our findings support the clinical effectiveness of tigecycline against commonly causative bacteria in COPD exacerbations and highlight its sufficient lung penetration in pulmonary infections of moderate severity.
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The purpose of the study was to evaluate painful procedures in ICU patients and to investigate their effect as well as the role of analgesia in the outcome. We measured pain level and vital signs before, during and after potentially painful procedures by using the Behavioral Pain Scale (BPS) and the Critical Care Pain Observation Tool (CPOT). We analyzed the correlation of these measurements and of analgesia with the outcome. Twenty-eight patients were subjected to 160 stimuli. There were statistically significant differences in pain scores and most vital signs between the different timepoints (before-during, during-after). Most of them were significantly correlated with each other. Physiotherapy proved to be the most painful procedure. Regarding the outcome, the administration of extra analgesia predicted less days of mechanical ventilation (p = 0.015) and of ICU stay (p = 0.016). The higher change in BPS was correlated with more days of mechanical ventilation [B (95% CI) = 3.640 (1.001-6.280), p = 0.007] and of ICU stay [B (95% CI) = 3.645 (1.035-6.254), p = 0.006]. The higher change in CPOT and the nonuse of extra analgesia were related to increased mortality [OR (95% CI) = 1.492 (1.107-2.011), p = 0.009 and OR (95% CI) = 2.626 (1.013-6.806), p = 0.047]. Increased pain in ICU patients was successfully assessed by the BPS and CPOT and correlated to worse outcomes, which the administration of extra analgesia might improve.
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Cuidados Críticos , Enfermedad Crítica , Humanos , Grecia , Reproducibilidad de los Resultados , Cuidados Críticos/métodos , Dolor , Unidades de Cuidados IntensivosRESUMEN
OBJECTIVES: Pulmonary involvement of varying etiology is common in collagen vascular diseases (CVDs). Bronchoalveolar lavage fluid (BALF) cell differentials reveal information on the immune mechanisms involved in the CVDs. The aim of the present study was to evaluate BALF cell populations in CVD-associated ILD and to investigate possible correlation with pulmonary function. METHODS: Fifty-seven patients (26 male and 31 female, mean age ± SD: 54.68±12.18 years) with CVD-associated interstitial lung disease were studied. Patients were divided into 6 groups based on underlying CVD. The study population also included a group of 10 healthy controls. BALF was examined in all individuals. Cell density, total cell number and differential cell count were recorded. BALF lymphocyte subsets were analysed by dual flow cytometry. Pulmonary function was assessed in all patients. RESULTS: BALF differential cell count did not differ significantly among the different groups. Scleroderma patients showed the highest percentage of CD19 cells (p<0.001). The NK and NKT cell percentages were significantly higher in systemic lupus erythematosus and in Sjögren, respectively, compared to other CVDs and controls (p=0.001 and p<0.001). Also BALF neutrophil percentage correlated negatively with FVC (r=-0.356, p=0.011) and FEV1 (r=-0.336, p=0.017) and BALF NKT cell percentage correlated negatively with pO2 (r=-0.415, p=0.003). CONCLUSIONS: Important variations observed in BALF cell populations suggest the implication of NK and NKT cells in the pathogenesis of lung involvement in CVDs.
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Enfermedades del Colágeno/inmunología , Células Asesinas Naturales/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Pulmón/inmunología , Enfermedades Vasculares/inmunología , Adulto , Anciano , Antígenos CD19/análisis , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Enfermedades del Colágeno/fisiopatología , Femenino , Citometría de Flujo , Volumen Espiratorio Forzado , Humanos , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Células T Asesinas Naturales/inmunología , Pruebas de Función Respiratoria , Enfermedades Vasculares/fisiopatología , Capacidad VitalRESUMEN
BACKGROUND: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. METHODS: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. RESULTS: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p<0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p<0.001, NSCLC: p=0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p<0.001, NSCLC: p=0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p>0.05). CONCLUSIONS: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.
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Aminofilina/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Intercambio de Cromátides Hermanas/efectos de los fármacos , Aminofilina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/genética , Células Cultivadas , Sinergismo Farmacológico , Femenino , Historia Medieval , Humanos , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVE: Data on natural killer (NK)- and natural killer T (NKT)- like cells in the immunopathogenesis of sarcoidosis remain limited. The aim was to assess NK- and NKT-like cells across different stages in bronchoalveolar lavage (BALF) versus peripheral blood (PB) in comparison to controls. METHODS: Forty four patients (32 women and 12 men, mean age 46.6±14.4 years) with biopsy-proven sarcoidosis and 10 healthy individuals (6 women, 4 men mean age 52.6±19.1 years) were submitted to BALF. Total cells and cell differentials were counted, while CD45+, CD3+, CD4+, CD8+, CD19+, CD3-CD16/56 (NK cells) and CD3+CD16/56+ (NKT-like cells) were determined by dual flow cytometry in BALF and PB. RESULTS: A significantly lower percentage of both NK and NKT-like cells was observed in BALF of controls and sarcoid patients (SP) compared to PB. Both BALF NK and NKT-cell counts were significantly higher in SP than in controls (NK: p=0.046, NKT-like: p=0.012) In addition BALF NK cell percentage differed among sarcoidosis stages (p=0.005). In PB NK-cell count was lower in sarcoidosis patients but the difference did not reach statistical significance. Also, in sarcoid patients' BALF NK-cell percentage negatively correlated with lymphocyte percentage (r=-0.962, p<0.001). CONCLUSIONS: The increased count of BALF NK and NKT-like cells in sarcoidosis compared to controls along with the increase of NK cells with stage progression are in line with a growing number of investigations suggesting the involvement of NK- and NKT-like cells in the pathogenesis of sarcoidosis.
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Background: The aim of the present study was the application of the latest phenotype recommendations in Greek patients, in order to identify specific clinical, imaging and spirometric characteristics, at initial diagnosis of sarcoidosis, related to disease phenotypes. Methods: Our cohort included 147 patients coming from Northern Greece, recruited from the Outpatient Sarcoidosis Clinic, of Aristotle University of Thessaloniki. The observation period was 5 years. The Scadding staging system and the World Association of Sarcoidosis and other Granulomatous Disorders (WASOG) Clinical Outcome Status instrument were used. Phenotypes were defined by the latest DELPHI consensus recommendations. Results: The following clinical phenotypes were identified: asymptomatic 59%, acute 14.3%, chronic 12.9% and advanced 33.3%. The observed phenotypes were not related to Scadding stages. Lung function decline was in line with phenotype severity. The presence of fibrosis to any extent upon diagnosis differed among phenotypes (asymptomatic 13.8%, acute 38.1%, chronic 57.9%, advanced 61.2%, P<0.001) and was common for relapsing patients (P<0.001). In spontaneously remitting patients, fibrosis upon diagnosis was found less often than in non-remitting patients (P<0.001). Renal involvement was more frequently found in the advanced phenotype (P=0.032). Skin involvement was more common for patients with acute onset (P<0.001) and spontaneous remission (P=0.012). Ocular involvement was mainly found in relapsing patients (P<0.001). Conclusions: In our cohort, sarcoidosis clinical phenotypes have certain clinical, imaging and functional characteristics, at initial diagnosis of the disease, which could be assessed in everyday practice.
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BACKGROUND: This study examined the drug-specific and overall adherence of teenagers and adults with cystic fibrosis (CF) to inhaled therapies, to assess the degree of adherence, stability over a period of 4 years, and its association with health outcomes. METHODS: Fifty-five participants (30 women and 25 men) aged 14 years or older from two CF centers were enrolled in a retrospective review of inhaled medication adherence over 4 years. Adherence was assessed by the number of doses that were obtained by each participant based on the "e-prescription.gr" platform and the calculation of the medication possession ratio (MPR). RESULTS: The mean composite MPR (cMPR) for the entire research period was 0.75 ± 0.19. A total of 43.4% of participants showed a variance of adherence <25%. Participants with stable adherence had a significantly higher mean cMPR compared with those with variable adherence (0.86 ± 0.16 vs. 0.66 ± 0.17, p < 0.001). A statistically significant difference between groups of patients with different degrees of mean cMPR and mean weight was observed (p = 0.011). Patients with a mean cMPR ≥0.80 weighed significantly more than those with moderate and low adherence. In addition, mean weight correlated significantly with the mean cMPR (Β [95% confidence interval] = 14.845 [0.191-29.498], r = 0.269, p = 0.047). CONCLUSIONS: In our setting, the cMPR was easy to assess and showed that adherence was probably better than expected. The association of cMPR with weight should be further investigated. Stable adherence seemed to be related to high adherence. This observation could enhance our understanding of people with CF and their approach to treatment.
Asunto(s)
Fibrosis Quística , Adolescente , Adulto , Fibrosis Quística/tratamiento farmacológico , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Estudios RetrospectivosRESUMEN
BACKGROUND: Adherence to pulmonary medication is pivotal in delaying the progression of lung disease in cystic fibrosis (CF). Further exploring the consequences of poor adherence and its impact on disease severity may be valuable to personalize CF treatment strategy. AIM: To evaluate indicators of disease severity among children and adults with CF and investigate which of them are related to pulmonary medication adherence. METHODS: This is a retrospective cohort study. Data of children and adults followed up in one pediatric and one adult CF Unit were evaluated over 4 years. Disease severity was assessed by measuring body mass index (BMI), lung function, history of pulmonary exacerbations, and medication complexity. Adherence was assessed by calculating a 12-month medication possession ratio (MPR) for each pulmonary medication and then averaged for a composite MPR (cMPR) for each patient. Regression analysis was performed to explore the association of adherence with disease severity. RESULTS: Ninety-five patients were included in our study, 52 children and 43 adults. The overall cMPR was 0.74 (SD = 0.25); 0.68 (SD = 0.24) for children and 0.81 (SD = 0.24) for adults. Adults presented higher adherence, with overall mean cMPR 0.81 (SD = 0.24) compared to children with mean cMPR 0.68 (SD = 0.24) (p < 0.05, 95% CI = -0.27 to -0.03). Adherence was inversely related to FEV1 % predicted (ß = -0.002, 95% CI = -0.004 to 0, p = 0.023) and FVC% predicted (ß = -0.003, 95% CI = -0.005 to -0.001, p = 0.006) in regression analysis. Adherence was not found to be associated with BMI, history of exacerbations and medication complexity. The analysis of each medication showed that adherence to Dornase-alpha, Tobramycin and Colomycin was significantly related to specific disease severity indicators. CONCLUSION: An overall moderate to high level of adherence was found among our study population. Adults presented higher adherence compared to children. FEV1% and FVC% predicted were related to a significant decrease in adherence. Among our group of CF patients with an overall moderate to high level of adherence, adherence to pulmonary medication was inversely related to disease severity.