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BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.
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Tratamiento Farmacológico de COVID-19 , Glucocorticoides/uso terapéutico , Prednisolona/uso terapéutico , Adulto , Anciano , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/virología , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal , Irán , Tiempo de Internación , Masculino , Persona de Mediana Edad , Prednisolona/efectos adversos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: We aimed to describe the epidemiological and clinical characteristics of Iranian patients with COVID-19. METHODS: In this single-center and retrospective study, patients with confirmed COVID-19 infections were enrolled. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with outcomes. RESULTS: Of 179 patients with confirmed COVID-19 infection, 12 remained hospitalized at the end of the study and 167 were included in the final analysis. Of these, 153 (91.6%) were discharged and 14 (8.38%) died in hospital. Approximately half (50.9%) of patients suffered from a comorbidity, with diabetes or coronary heart disease being the most common in 20 patients. The most common symptoms on admission were fever, dyspnea, and cough. The mean durations from first symptoms to hospital admission was 8.64 ± 4.14 days, whereas the mean hospitalization time to discharge or death was 5.19 ± 2.42 and 4.35 ± 2.70 days, respectively. There was a significantly higher age in non-survivor patients compared with survivor patients. Multivariate regression showed increasing odds ratio (OR) of in-hospital death associated with respiratory rates >20 breaths/min (OR: 5.14, 95% CI: 1.19-22.15, p = 0.028) and blood urea nitrogen (BUN) >19 mg/dL (OR: 4.54, 95% CI: 1.30-15.85, p = 0.017) on admission. In addition, higher respiratory rate was associated with continuous fever (OR: 4.08, 95% CI: 1.18-14.08, p = 0.026) and other clinical symptoms (OR: 3.52, 95% CI: 1.05-11.87, p = 0.04). CONCLUSION: The potential risk factors including high respiratory rate and BUN levels could help to identify COVID-19 patients with poor prognosis at an early stage in the Iranian population.
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COVID-19 , Comorbilidad , Hospitalización , Humanos , Irán/epidemiología , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
OBJECTIVE: This study investigated the efficacy and safety of supplementation with probiotics in improving chronic pulmonary symptoms due to sulfur mustard (SM) exposure. METHODS: In a randomized double-blind placebo-controlled study, 65 subjects suffering from chronic pulmonary complications of SM were assigned to one probiotic capsule (1 × 109 CFU containing seven strains of lactic acid-producing bacteria) every 12 h or an identical placebo for six weeks. Serum high-sensitivity C-reactive protein (CRP) concentrations, pulmonary function tests (FEV1, FEV1/FVC and MMEF 25-75%) and COPD assessment test (CAT) were assessed at baseline and at the end of trial. RESULTS: The groups were comparable in baseline characteristics. There were significant improvements in FEV1/FVC in the probiotic but not in placebo group. CAT scores were decreased in both study groups. However, between-group comparison of changes in the assessed parameters reached statistical significance only for CAT score (p < 0.001). There was no report of adverse events during the course of trial. CONCLUSIONS: Findings of the present trial favor the efficacy of probiotic supplementation in improving the pulmonary symptoms of SM-exposed subjects.
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Sustancias para la Guerra Química/toxicidad , Gas Mostaza/toxicidad , Probióticos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Calidad de Vida , Adulto , Suplementos Dietéticos , Método Doble Ciego , Humanos , Irán , Masculino , Probióticos/administración & dosificación , Probióticos/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Pruebas de Función Respiratoria , Encuestas y Cuestionarios , Resultado del Tratamiento , Veteranos , Salud de los VeteranosRESUMEN
PURPOSE: Sulfur mustard (SM) lung is a heterogeneous disease associated with abnormal inflammatory immune responses. The Th17/Treg axis imbalance is associated with the pathogenesis of chronic inflammatory pulmonary disease. We aimed to determine the distribution of different Th17 and Treg cells in patients with SM lung and chronic obstructive pulmonary disease (COPD) and evaluate the clinical implications in this homeostasis. METHODS: In this analytical cross-sectional study, CD4 (+) Foxp3(+ )Treg and CD4(+) IL-17(+ )Th17 cells were measured in peripheral blood mononuclear cells (PBMCs) and transbronchial biopsy (TBB) samples of 15 SM-exposed patients, 12 COPD and 13 healthy controls (HCs). The potential correlation between the ratio of Th17/Tregs and lung function was evaluated with multivariate logistic regression (MLR) analysis. RESULTS: The frequency of CD4 (+) FoxP3(+) Tregs and CD4 (+) IL-17(+) Th17 was increased â¼1.7-fold (8.71/4.95) and â¼2.7-fold (1.028/0.371) respectively, in the PBMC of SM patients compared with the health controls (p < 0.001). The results indicated that there were increases in the frequency of Th17 and Tregs cells in the patients with COPD versus the HC, that is, â¼2.6-fold (0.987/0.371) and â¼1.4-fold (7.12/4.95), respectively; but they did not reach to SM level (p ≥ 0.05). Moreover, in the TBB samples, the CD4 (+) IL-17(+ )Th17 and CD4(+) FoxP3(+ )Tregs numbers were significantly higher in SM and COPD patients than HC (p < 0.05). The Th17 and Treg cells were inversely correlated with forced expiratory volume in 1s (FEV1%) (r = -0.351, p = 0.001; r = -0.344, p = 0.021) and FEV1/FVC (r = -0.44, p = 0.001; r = -0.302, p = 0.011), respectively. Instead, positive correlations were found between Treg/Th17 ratios and forced FEV1%pred (r = 0.156, p = 0.007), as well as FEV1/FVC ratio (r = 0.334, p = 0.006). CONCLUSIONS: The imbalance of Th17/Treg has a key role in immunopathogenesis of chronic phase of mustard lung disease.
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Enfermedades Pulmonares/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/inmunología , Femenino , Factores de Transcripción Forkhead/inmunología , Humanos , Interleucina-17/inmunología , Leucocitos Mononucleares , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Gas Mostaza/toxicidad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
INTRODUCTION: Sleep-related breathing disorders are associated with unusual respiratory pattern or an abnormal reduction in gas exchange during sleep that is common in sulfur mustard (SM) exposure. METHODS: We compared 57 Iranian male patients injured with SM and had any complaints of sleep problems with an age-matched group of 21 Iranian male patients who had complaints of sleep problems and were not chemically injured; this group had Epworth Sleepiness Scale (ESS) above 10 and whom referred for polysomnography. Split-night studies were performed for patients with diagnostic polysomnography for obstructive sleep apnea (OSA) and respiratory events. We then studied respiratory events including episodes of OSA, apnea-hypopnea index (AHI) and respiratory disturbance index (RDI). RESULTS: The mean age in mustard-exposed patients was 48.14±8.04 years and in age-matched group, 48.19±8.39 years. In mustard exposed patients, there were statistical differences for the episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001) between two segments of split-night studies. In the age-matched group, there were statistically differences for each parameter (episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001)). There were no significant differences between two groups. CONCLUSION: This study indicated that the incidence of respiratory events and nocturnal hypoxemia during sleep in mustard-exposed patients were high and treatment with CPAP significantly reduced all these events.
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Presión de las Vías Aéreas Positiva Contínua , Personal Militar , Gas Mostaza/envenenamiento , Síndromes de la Apnea del Sueño/inducido químicamente , Síndromes de la Apnea del Sueño/terapia , Adulto , Estudios de Casos y Controles , Sustancias para la Guerra Química/envenenamiento , Humanos , Irán , Masculino , Persona de Mediana Edad , Polisomnografía/efectos de los fármacos , Síndromes de la Apnea del Sueño/diagnóstico , GuerraRESUMEN
Late respiratory complications in patients suffering from pulmonary lesions due to sulfur mustard (SM) gas are asthma, chronic obstructive pulmonary disease and bronchiectasis. Recently PON1 antioxidant activity draws attention as the enzyme which prevents the oxidation of lipoproteins during oxidative stress. In this study we aimed to investigate PON1 192 polymorphisms and paraoxonase and arylesterase activity in the serum of SM-exposed lung disease patients. Also, we examined the detection of PON1 and apoA1 proteins in BAL fluid. 101 male patients were included who were categorized to three groups of mild, moderate and severe suffering from pulmonary lesions due to SM. Significant reduction in paraoxonase activity [Healthy: 412.46 ± 89.1 U/L, Severe: 89.66 ± 20.7 U/L] (p < 0.0001) and arylesterase activity [Healthy: 25826.4 ± 4425.23 U/L, Severe: 16760.43 ± 3814.9 U/L] (p < 0.0001) with increase in severity of disease was demonstrated statistically. With respect to the distribution of the PON1 polymorphism, the RR genotype was more frequent in severe patients [37.2%] than healthy group [10%] (p < 0.05) and no significant regression was found between genotype and PON1 activity. On the other hand, the results of PON1 and apoA1 detection illustrated that only apoA1 protein was found in BAL fluid. According to our findings it seems that increase in the stress oxidative in chemical injured veterans with pulmonary complications comes with reduction in PON1 enzyme activity and appearance of RR genotype rises up with the increase in disease severity. Since a significant correlation between enzyme activity and genotype was not observed altering these two variables with each other requires more studies.
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Arildialquilfosfatasa/genética , Sustancias para la Guerra Química/toxicidad , Enfermedades Pulmonares/genética , Gas Mostaza/toxicidad , Polimorfismo Genético , Índice de Severidad de la Enfermedad , Adulto , Apolipoproteína A-I/análisis , Arildialquilfosfatasa/sangre , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Peroxidación de Lípido/genética , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/enzimología , Masculino , Persona de Mediana Edad , Estrés Oxidativo/genética , Pruebas de Función Respiratoria , Triglicéridos/sangreRESUMEN
INTRODUCTION: Mustard gas has serious adverse effects on several organs and functions in humans. In this study, we analyzed potential correlations between obstructive airway disease and sleep disorders in Iranian mustard gas-injured patients. METHODS: We enrolled 30 male mustard gas-injured veterans and civilians from the Chemical Warfare Exposure Clinic at Baqiyatallah Hospital, Tehran. All the subjects underwent comprehensive polysomnographic and spirometric evaluations for diagnosis of sleep disorders. Patients were categorized into three groups according to the severity of their obstructive airway disease based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria: group 1 (GOLD I and II), group 2 (GOLD III), and group 3 (GOLD IV). RESULTS: Patients with less severe obstructive airway disease had significantly higher rate of hypopnea (p = 0.05) and AHI (p = 0.05). The number of REM events was significantly higher in patients with less severe airway disease (p = 0.028). Stage 1 sleep among patients with higher FEV1 significantly constituted a higher proportion of sleep, and stage 4 sleep was significantly longer in patients with higher DLCO (p = 0.043, both). CONCLUSION: We found that sleep parameters in SM-exposed patients have some relations with spirometric parameters. Future studies with large patient populations are needed for confirmation of our results, and therapeutic interventions are needed to evaluate endeavors we can do to enhance health and quality of life in our mustard gas-injured population.
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Sustancias para la Guerra Química/toxicidad , Gas Mostaza/toxicidad , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Veteranos , Adulto , Nivel de Alerta/efectos de los fármacos , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Irán , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana Edad , Polisomnografía/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Apnea Central del Sueño/inducido químicamente , Apnea Central del Sueño/diagnóstico , Apnea Obstructiva del Sueño/inducido químicamente , Apnea Obstructiva del Sueño/diagnóstico , Sueño REM/efectos de los fármacos , Espirometría , Estadística como AsuntoRESUMEN
OBJECTIVE: Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. METHOD: This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. RESULTS: Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. CONCLUSION: Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.
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Background: Chronic obstructive pulmonary disease (COPD) as one of the health-threatening problems imposes many economic costs on health systems. Today, there is a greater tendency to use complementary and alternative therapies in the treatment of diseases. This study aimed to evaluate the efficacy of a Persian herbal formulation in patients with COPD. Materials and Methods: This randomized clinical trial was conducted on 76 patients with mild-severe COPD assigned to 2 groups (in each group n=38) for 8 weeks. The interventional group received Compound Honey Syrup (CHS), consisting of combination of honey and extracts of five medicinal plants (i.e., ginger, cinnamon, saffron, cardamom, and galangal) and the control group received a placebo. The COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ), and lung function test were used before and after. Results: Seventy-six patients, 88.6% male and 55.7% under 60 years of age, completed the course of treatment. At the end of the study, the overall score of the CAT questionnaire was significantly different between the first and fourth week (P=0.029). Meanwhile the findings of SGRQ questionnaire were significantly different between the interventional and control groups at other times (P=0.001). FEV1 and FEV1/FVC were found to be significantly different between two groups in weeks 4 and 8 (P <0.05). At the end of the study, no side effects of CHS were reported. Conclusion: Based on the data presented herein, CHS could be effective as a complementary and safe drug in increasing the quality of life of with COPD.
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BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.
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Amidas/administración & dosificación , Amidas/efectos adversos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19 , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Intubación , Estimación de Kaplan-Meier , Tiempo de Internación , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Cancer is one of the most widespread challenges and important diseases, which has the highest mortality rate. Lung cancer is the most common type of cancer, so that about 25% of all cancer deaths are related to the lung cancer. The lung cancer is classified as two different types with different treatment methodology: the small cell lung carcinoma and nonsmall cell lung carcinoma are two categories of the lung cancer. Since the lung cancer is often in the latent period in its early stages, therefore, early diagnosis of lung cancer has many challenges. Hence, there is a need for sensitive and reliable tools for preclinical diagnosis of lung cancer. Therefore, many detection methods have been employed for early detection of lung cancer. As lung cancer tumors growth in the body, the cancerous cells release numerous DNA, proteins, and metabolites as special biomarkers of the lung cancer. The levels of these biomarkers show the stages of the lung cancer. Therefore, detection of the biomarkers can be used for screening and clinical diagnosis of the lung cancer. There are numerous biomarkers for the lung cancer such as EGFR, CEA, CYFRA 21-1, ENO1, NSE, CA 19-9, CA 125 and VEGF. Nowadays, electrochemical methods are very attractive and useful in the lung cancer detections. So, in this paper, the recent advances and improvements (2010-2018) in the electrochemical detection of the lung cancer biomarkers have been reviewed.
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Biomarcadores de Tumor/análisis , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Neoplasias Pulmonares/diagnóstico , Animales , HumanosRESUMEN
BACKGROUND: There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient's outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19). METHODS: This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient's data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir. RESULTS: The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001). CONCLUSION: This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. Graphical abstract.
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Tratamiento Farmacológico de COVID-19 , Hospitalización/estadística & datos numéricos , Neumonía Viral/tratamiento farmacológico , Adulto , Anciano , Azitromicina/administración & dosificación , COVID-19/complicaciones , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Irán , Tiempo de Internación , Levofloxacino/administración & dosificación , Lopinavir/administración & dosificación , Masculino , Meropenem/administración & dosificación , Persona de Mediana Edad , Naproxeno/administración & dosificación , Oseltamivir/administración & dosificación , Neumonía Viral/virología , Prednisolona/administración & dosificación , Estudios Retrospectivos , Ritonavir/administración & dosificación , Resultado del Tratamiento , Vancomicina/administración & dosificaciónRESUMEN
The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1ß, IL-18, and IL-1ßR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Sustancias para la Guerra Química/efectos adversos , Inflamasomas/metabolismo , Interleucina-1/metabolismo , Enfermedades Pulmonares/inmunología , Gas Mostaza/efectos adversos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Mediadores de Inflamación/sangre , Interleucina-1/sangre , Interleucina-1/genética , Interleucina-18/sangre , Guerra de Irak 2003-2011 , Enfermedades Pulmonares/inducido químicamente , Masculino , Persona de Mediana Edad , Proteínas NLR , Enfermedad Pulmonar Obstructiva Crónica/inmunología , VeteranosRESUMEN
Sulfur mustard (SM) is a toxic agent that targets several tissues. It is the leading cause of persistent lung disease, progressive deterioration in lung function, and mortality among injured patients. Disturbed sleep and poor quality of sleep are common in SM-exposed patients with chronic respiratory problems. Melatonin is an alternative medication that has been widely used to treat poor sleep quality caused by several specific conditions. This study aimed to evaluate the efficacy of melatonin administration in improvement of sleep quality in SM-injured patients. In this randomized, double-blind and placebo-controlled trial study a total of 30 SM-exposed male patients were recruited. Patients received 3 mg melatonin (N = 15) or placebo (N = 15), orally in a single dose, 1 h before bedtime for 56 consecutive days. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnea was determined by STOP-Bang questionnaire. Compared with placebo, melatonin administration significantly improved global PSQI score, particularly sleep latency (P = 0.03) and subjective sleep quality (P = 0.004). Mean of global PSQI score was declined significantly (P = 0.01) from 10.13 ± 3.44 to 6.66 ± 3.08 in melatonin group. No differences in ESS and STOP-Bang scores were observed between two groups. Melatonin was effective in improving global PSQI score and sleep latency, but not daytime sleepiness and obstructive sleep apnea in SM-exposed patients. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.
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The long lasting inflammation and immune dysregulation is one of the main mechanisms involved in lung complication of veterans exposed to sulfur mustard (SM) gas. Th17/Treg cells have an important role in immunopathogenesis of chronic obstructive pulmonary disease (COPD) and mustard lung disease. In this study, expression of cytokines genes levels related to Th17/Treg cells was determined in peripheral blood mononuclear (PBMC) of mustard lung patients and was compared with COPD patients and healthy controls (HC). Real time-polymerase chain reaction was used to assay genes expression levels of Th17 related cytokines (IL-17, IL-6 and TGF-ß) and Treg related cytokines (IL-10, TGF-ß). IL-17 gene expression level considerably was higher in SM patients (9.98±0.65, p<0.001), and COPD (4.75±0.71, p<0.001), compare to HC group. Also, gene expression level of IL-6 in the SM group (3.31±0.93, p<0.001) and COPD group (2.93±0.21, p<0.001) were significantly higher than the HC group. The IL-10 gene expression level showed a high increase in SM patients (4.12±0.91, p<0.01), and COPD (2.1±0.45, p<0.01). Finally, the TGF-ß gene expression level was increased in SM patients (4.91±0.69, p<0.001) as well as in COPD group (5.41±0.78, p<0.001). In SM patients, IL-17 (R=-0.721, p<0.05), IL-6 (R=-0.621, p<0.05) and TGF-ß (R=-0.658, p<0.05) had significant negative association with FEV1 (%). Inversely, Il-10 showed positive correlation (R=0.673) with FEV1 (%). Th17/Treg cells related cytokines genes were highly expressed and imbalanced in peripheral blood mononuclear cells of SM and COPD patients which correlated with pulmonary dysfunction.
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Citocinas/genética , Expresión Génica , Gas Mostaza/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Citocinas/metabolismo , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Persona de Mediana Edad , ARN Mensajero/genética , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Linfocitos T Reguladores/inmunología , Células Th17/inmunologíaRESUMEN
Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.
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Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Redes Reguladoras de Genes , Neoplasias Pulmonares/metabolismo , Fumar/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Niño , Femenino , Estudios de Seguimiento , Ontología de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Proteómica , Transducción de Señal , Fumar/genética , Fumar/patología , Adulto JovenRESUMEN
Sulfur mustard (SM) is a potent alkylating agent that targets several organs, especially lung tissue. Although pathological effects of SM on mustard lung have been widely considered, molecular and cellular mechanisms for these pathologies are poorly understood. We investigated changes in expression of genes related to oxidative stress (OS) and antioxidant defense caused by SM in lung tissue of patients. We performed gene expression profiling of OS and antioxidant defense in lung tissue samples from healthy controls (n=5) and SM-exposed patients (n=6). Changes in gene expression were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in cellular OS response. 47 (55.95%) genes were found to be significantly upregulated in patients with mustard lung compared with controls (p<0.05), whereas 7 (8.33%) genes were significantly downregulated (p<0.05). Among the most upregulated genes were OS responsive-1 (OXSR1), forkhead box M1 (FOXM1), and glutathione peroxidase-2 (GPX2), while metallothionein-3 (MT3) and glutathione reductase (GSR) were the most downregulated genes. Expression of hypoxia-induced genes (CYGB and MB), antioxidants and reactive oxygen species (ROS)-producing genes were significantly altered, suggesting an increased oxidative damage in mustard lungs. Mustard lungs were characterized by hypoxia, massive production of ROS, OS, disruption of epithelial cells, surfactant dysfunction, as well as increased risk of lung cancer and pulmonary fibrosis. Oxidative stress induced by ROS is the major mechanism for direct effect of SM exposure on respiratory system. Antioxidant treatment may improve the main features of mustard lungs.
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Antioxidantes/metabolismo , Pulmón/efectos de los fármacos , Gas Mostaza/envenenamiento , Estrés Oxidativo/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Adulto , Anciano , Sustancias para la Guerra Química/envenenamiento , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Epitelio/patología , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Hipoxia , Pulmón/metabolismo , Pulmón/patología , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-γ on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SM-induced complications. Patients (n = 15) were administered IFNγ (100 µg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNγ, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-α], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-ß] parameters were performed at baseline and at trial end. The results indicated that IFNγ therapy is associated with improvements in SGRQ (p < 0.001) and CAT (p < 0.001) scores, decreased severity of cough (p = 0.001), dyspnea (p < 0.001), and morning dyspnea (p < 0.001), reduced frequency of sputum production (p < 0.001) and hemoptysis (p < 0.001), and elevated FEV1 (p = 0.065). Serum levels of IL-4 (p < 0.001), IL-6 (p < 0.001), IL-10 (p < 0.001), CGRP (p < 0.001), MMP-9 (p = 0.001), TNFα (p < 0.001), TGFß (p < 0.001) and MDA (p = 0.001) were decreased while those of IL-2 (p < 0.001), IFNγ (p < 0.001), and both total (p = 0.005) and reduced glutathione (p = 0.061) increased by the end of the trial. It was concluded that IFNγ has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM-induced pulmonary complications. A modulation of cytokines and oxidative stress appears responsible for the clinical efficacy of IFNγ.
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Inmunoterapia/métodos , Interferón gamma/administración & dosificación , Enfermedades Pulmonares/terapia , Gas Mostaza/toxicidad , Intoxicación/terapia , Adulto , Péptido Relacionado con Gen de Calcitonina/sangre , Enfermedad Crónica , Citocinas/sangre , Humanos , Inyecciones Subcutáneas , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/inmunología , Estrés Oxidativo/efectos de los fármacos , Intoxicación/complicaciones , Intoxicación/inmunología , Calidad de Vida , Pruebas de Función Respiratoria , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in) equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic measures and depressive symptoms in Iranian veterans with chemical injuries. METHODS: In this pilot study, 35 Iranian veterans with chemical injuries complaining of a sleep problem were selected. Initially, participants were evaluated via all-night polysomnography, then, they completed the research questionnaires. Collected data were analyzed using Pearson correlation coefficients. RESULTS: Data analyses showed that there was no significant correlation between many of self-reposted variables and polysomnogaphic recordings, however, remarkable relationships were found between the Pittsburgh Sleep Quality Index and the Beck Depression Inventory scores. CONCLUSION: The findings indicated that sleep complaints of chemically-injured veterans are not equivalent to objective sleep disturbances, however, these complaints are largely associated with level of depression. This study emphasizes the important role of mood in sleep evaluation. Further, the findings suggest using a combination of both subjective and objective measures for accurate assessment of sleep quality in Iranian veterans with chemical injuries (i.e., multimethod approach).