COPD patient profiles in primary care. Referral criteria.

COPD is a disease with a high prevalence that diminishes the quality of life of many patients. Despite this, there are still high rates of under-diagnosis in Spain, partly due to a lack of recognition of the pathology by patients. In this context, the role played by primary care teams becomes fundamental, as they are one of the first lines of entry into the health system. In this paper we explain the different COPD profiles that may be present, and update the tools for diagnosis and treatment, which, together with an attitude of active suspicion of the disease, can help in the correct management of patients, whether they are undiagnosed or have subsequent complications.

Polystyrene nanoplastics in the marine mussel Mytilus galloprovincialis.

Concerns about plastic pollution and its toxicity towards animals and people are growing. Polystyrene (PS) is a plastic polymer highly produced in Europe for packaging purposes and building insulation amongst others. Whatever their source-illegal dumping, improper waste management, or a lack of treatment for the removal of plastic debris from wastewater treatment plants-PS products ultimately end up in the marine environment. Nanoplastics (<1000 nm) are the new focus for plastic pollution, gaining broad interest. Whether primary or secondary, their small size permits nanoparticles to cross cellular boundaries, consequently leading to adverse toxic effects. An in vitro assay of Mytilus galloprovincialis haemocytes exposed to 10 µg/L of polystyrene nanoplastics (PS-NPs; 50 nm) for 24 h was used to test cellular viability along with the luminescence inhibition (LC50) of Aliivibrio fischeri bacteria to evaluate acute toxicity. Cellular viability of mussel haemocytes decreased significantly after a 24 h exposure and PS-NPs LC50 range from 180 to 217, µg/L. In addition, a 28-day exposure of the marine bivalve M. galloprovincialis to PS-NPs (10 µg/L; 50 nm) was performed to evaluate the neurotoxic effects and the uptake of these plastic particles in three bivalve tissues (gills, digestive gland, and gonads). The ingestion of PS-NPs was time- and tissue-specific, suggesting that PS-NPs are ingested through the gills and then translocated through the mussel bloodstream, to the digestive gland and gonads where the highest amount of ingested PS-NPs was reported. Ingested PS-NPs may compromise the digestive glands' key metabolic function and impair mussels' gametogenic and reproductive success. Data on acetylcholinesterase inhibition and those previously obtained on a wide range of cellular biomarkers were elaborated through weighted criteria providing a synthetic assessment of cellular hazard from PS-NPs.

Ecotoxicity of emerging contaminants in the reproductive organ of marine mussels Mytilus galloprovincialis.

Contaminants of emerging concern (CECs) present a new threat to the marine environment, and it is vital to understand the interactions and possible toxicity of CEC mixtures once they reach the ocean. CECs-such as metal nanoparticles, nanoplastics, and pharmaceuticals-are groups of contaminants some of which have been individually evaluated, though their interactions as mixtures are still not fully understood. To ensure a healthy and prosperous future generation, successful reproduction is key: however, if hindered, population dynamics may be at danger leading to a negative impact on biodiversity. This study aimed to understand the effects of silver (20 nm nAg, 10 µg/L), polystyrene nanoparticles (50 nm nPS, 10 µg/L), and 5-fluorouracil (5FU, 10 ng/L) individually and as a mixture (10 µg/L of nPS + 10 µg/L of nAg +10 ng/L of 5FU) in the gonads of Mytilus galloprovincialis. A multibiomarker approach, namely the antioxidant defence system (ADS; superoxide dismutase, catalase, glutathione peroxidases, glutathione - S - transferases activities), and oxidative damage (OD; lipid peroxidation) were analysed in the gonads of mussels. All exposure treatments after 3 days led to an increase of enzymatic activity, followed by an inhibition after 14 and 21 days. Thus, ADS was overwhelmed due to the generation of ROS, resulting in OD, except for nPS exposed mussels. The OD in Mix exposed mussels increased exponentially by 57-fold. When CEC mixtures interact, they are potentially more hazardous than their individual components, posing a major threat to marine species. To understand synergistic and antagonistic interactions, a model was applied, and antagonistic interactions were observed in evaluated biomarkers at all time-points, apart from a synergistic interaction at day 3 relative to LPO. Results indicate that the effects observed in Mix-exposed mussel gonads are mainly due to the interaction of nAg and 5FU but not nPS.

Valoración ecográfica de la dinámica diafragmática en pacientes con enfermedad pulmonar obstructiva crónica tras tratamiento con indacaterol/glicopirronio / Ultrasound assessment of diaphragmatic dynamics in patients with chronic obstructive pulmonary disease after treatment with indacaterol/glycopyrronium

Introduction Air trapping is one of the main determinants of dyspnea in patients with chronic obstructive pulmonary disease (COPD). An increase in air trapping leads to a change in the normal diaphragmatic configuration with associated functional impairment. Said deterioration improves with bronchodilator therapy. Chest ultrasound (CU) has been used to assess changes in diaphragmatic motility after short-acting bronchodilator therapy, but there are no previous studies on these changes after long-acting bronchodilator treatment. Material and methods Interventional prospective study. Patients with COPD and moderate to very severe ventilatory obstruction were included in the study. Diaphragm motion and thickness were assessed by CU before and after 3 months of treatment with indacaterol/glycopirronium 85/43 mcg. Results Thirty patients were included (56.6% men, mean age: 69.4 ± 6.2 years). Pre- and post-treatment diaphragmatic mobility measured during resting breathing, deep breathing, and nasal sniffing were 19.9 ± 7.1 mm and 26.4 ± 8.7 mm (p < 0.0001); 42.5 ± 14.1 mm and 64.5 ± 25.9 mm (p < 0.0001); and 36.5 ± 17.4 mm and 46.7 ± 18.5 mm (p = 0.012), respectively. A significant improvement was also found in the minimum and maximum diaphragm thickness (p < 0.05), but there were no significant changes in the diaphragmatic shortening fraction after treatment (p = 0.341). Conclusions Treatment with indacaterol/glycopyrronium 85/43 mcg every 24 hours for 3 months improved diaphragmatic mobility in patients with COPD with moderate to very severe airway obstruction. CU may be useful for assessing the response to treatment in these patients (AU)

Introducción El atrapamiento aéreo en la enfermedad pulmonar obstructiva crónica (EPOC) es uno de los principales responsables de la disnea en estos enfermos. Su incremento conlleva que el diafragma pierda su configuración habitual y se afecte así su funcionalidad, la cual parece mejorar tras la administración de terapia broncodilatadora. La ecografía torácica (ET) se ha utilizado para evaluar estos cambios tras el uso de broncodilatadores de acción corta, pero no hay estudios que valoren estas variaciones con el empleo de broncodilatadores de acción larga. Material y métodos Estudio prospectivo intervencionista de 3 meses de seguimiento donde se valoró el movimiento/grosor diafragmático con ET antes y después del inicio del tratamiento con indacaterol/glicopirronio 85/43 mcg en pacientes EPOC con obstrucción moderada-muy grave al flujo aéreo. Resultados Treinta pacientes fueron incluidos (56,6% hombres, edad media: 69,4 ± 6,2 años). La movilidad diafragmática pre y postratamiento en respiración a volumen corriente, profunda y sniff nasal fue de 19,9 ± 7,1 mm y 26,4 ± 8,7 mm (p < 0,0001), 42,5 ± 14,1 mm y 64,5 ± 25,9 mm (p < 0,0001) y 36,5 ± 17,4 mm y 46,7 ± 18,5 mm (p = 0,012), respectivamente. También existió una mejora significativa en el grosor diafragmático mínimo y máximo (p < 0,05) pero no en la fracción de engrosamiento diafragmático tras tratamiento (p = 0,341). Conclusione El tratamiento con indacaterol/glicopirronio 85/43 mcg cada 24 horas durante 3 meses mejoró la movilidad diafragmática en paciente con EPOC con obstrucción moderada-muy grave al flujo aéreo. La ET puede ser útil en la valoración de la repuesta al tratamiento de estos pacientes (AU)

Ultrasound assessment of diaphragmatic dynamics in patients with chronic obstructive pulmonary disease after treatment with indacaterol/glycopyrronium.

INTRODUCTION: Air trapping is one of the main determinants of dyspnea in patients with chronic obstructive pulmonary disease (COPD). An increase in air trapping leads to a change in the normal diaphragmatic configuration with associated functional impairment. Said deterioration improves with bronchodilator therapy. Chest ultrasound (CU) has been used to assess changes in diaphragmatic motility after short-acting bronchodilator therapy, but there are no previous studies on these changes after long-acting bronchodilator treatment. MATERIAL AND METHODS: Interventional prospective study. Patients with COPD and moderate to very severe ventilatory obstruction were included in the study. Diaphragm motion and thickness were assessed by CU before and after 3 months of treatment with indacaterol/glycopirronium 85/43 mcg. RESULTS: Thirty patients were included (56.6% men, mean age: 69.4 ± 6.2 years). Pre- and post-treatment diaphragmatic mobility measured during resting breathing, deep breathing, and nasal sniffing were 19.9 ± 7.1 mm and 26.4 ± 8.7 mm (p < 0.0001); 42.5 ± 14.1 mm and 64.5 ± 25.9 mm (p < 0.0001); and 36.5 ± 17.4 mm and 46.7 ± 18.5 mm (p = 0.012), respectively. A significant improvement was also found in the minimum and maximum diaphragm thickness (p < 0.05), but there were no significant changes in the diaphragmatic shortening fraction after treatment (p = 0.341). CONCLUSIONS: Treatment with indacaterol/glycopyrronium 85/43 mcg every 24 hours for 3 months improved diaphragmatic mobility in patients with COPD with moderate to very severe airway obstruction. CU may be useful for assessing the response to treatment in these patients.

New synthetic nano-immunotherapy (OncoTherad®) for non-muscle invasive bladder cancer: Its synthesis, characterization and anticancer property.

Bacillus Calmette-Guérin (BCG)-based intravesical immunotherapy has been applied as gold standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) for almost half a century. However, several patients with high-risk disease experience relapse, including those whose condition has worsened and who failed to respond to BCG. Non-significant therapeutic options have been developed for these at-risk patients, for many years. Immunotherapies have shown promising outcomes for bladder cancer treatment. Accordingly, our research group developed the OncoTherad® (MRB-CFI-1) immunotherapy, which has shown positive outcomes in NMIBC treatment. The aim of the current study is to describe, in details, the physicochemical features and potential action mechanisms of OncoTherad® nano-immunotherapy, based on toll-like receptor 4 (TLR4)-mediated interferon and on RANK/RANKL signaling pathways, in animal model with NMIBC. Based on the current findings, OncoTherad® nano-immunotherapy did not have genotoxic effect on the investigated model and did not show signs of limiting local and/or systemic toxicity at therapeutic doses. OncoTherad® nano-immunotherapy was more effective than the BCG treatment, since it reduced by 70% the malignancy rate. Furthermore, it was possible identifying an important action mechanism of OncoTherad®, which was based on the modulation of TLR4-mediated interferon and RANK/RANKL signaling pathways that, altogether, were essential to reduce malignancy rate. OncoTherad® mechanisms in these pathways helped preventing tumor recurrence.

Discordancia del tratamiento de la enfermedad pulmonar obstructiva crónica según la guía GesEPOC vs. GOLD / Discordance in treatment of chronic obstructive pulmonary disease following GesEPOC Guideline vs. GOLD

Introducción En España, el tratamiento farmacológico de la enfermedad pulmonar obstructiva crónica se basa en la Global Initiative for Chronic Obstructive Lung Disease (GOLD) y la Guía española de la enfermedad pulmonar obstructiva crónica (GesEPOC). El objetivo principal de este estudio fue evaluar la concordancia entre los tratamientos de inicio asignados por GOLD y GesEPOC. Material y métodos Estudio de simulación. Se emplearon las siguientes variables: FEV1%, exacerbaciones, disnea inicial, eosinofilia en sangre, antecedente de asma y grado de reversibilidad en la prueba broncodilatadora. Cuatro neumólogos clasificaron/asignaron un tratamiento a cada paciente (2 de ellos según GOLD y 2 según GesEPOC). Se calculó el coeficiente Kappa de Cohen global. Resultados Se incluyeron 467 pacientes. La concordancia entre el tratamiento recomendado por GOLD y GesEPOC fue pobre (Kappa: 0,17, IC 95%: 0,12-0,23). Conclusión Existe una pobre concordancia entre GOLD y GesEPOC a la hora de iniciar tratamiento en los pacientes con enfermedad pulmonar obstructiva crónica (AU)

Introduction Pharmacological treatment of chronic obstructive pulmonary disease in Spain is usually chosen according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or Spanish guidelines for chronic obstructive pulmonary disease (GesEPOC). The main objective of this study was to evaluate the degree of concordance between treatment for newly diagnosed chronic obstructive pulmonary disease patients according to GOLD and GesEPOC. Material and methods Simulation study. The following variables were used: FEV1%, exacerbations, dyspnoea at first evaluation, blood eosinophilia, personal history of asthma, and degree of bronchodilator reversibility. Four investigators classified and assigned a treatment to each patient (2 using GOLD criteria and the other 2 using GesEPOC). Global Kappa index was calculated. Results The database included 467 patients. Agreement between treatment decided using GOLD and GesEPOC was poor (Kappa: 0.17, 95% CI: 0.12-0.23). Conclusion There is a poor agreement between GOLD and GesEPOC recommendations for initial chronic obstructive pulmonary disease treatment (AU)

Discordance in treatment of chronic obstructive pulmonary disease following GesEPOC guideline vs. GOLD.

INTRODUCTION: Pharmacological treatment of chronic obstructive pulmonary disease in Spain is usually chosen according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or Spanish guidelines for chronic obstructive pulmonary disease (GesEPOC). The main objective of this study was to evaluate the degree of concordance between treatment for newly diagnosed chronic obstructive pulmonary disease patients according to GOLD and GesEPOC. MATERIAL AND METHODS: Simulation study. The following variables were used: FEV1%, exacerbations, dyspnoea at first evaluation, blood eosinophilia, personal history of asthma, and degree of bronchodilator reversibility. Four investigators classified and assigned a treatment to each patient (2 using GOLD criteria and the other 2 using GesEPOC). Global Kappa index was calculated. RESULTS: The database included 467 patients. Agreement between treatment decided using GOLD and GesEPOC was poor (Kappa: 0.17, 95% CI: 0.12-0.23). CONCLUSION: There is a poor agreement between GOLD and GesEPOC recommendations for initial chronic obstructive pulmonary disease treatment.

Prognostic value of lung ultrasound and its link with inflammatory biomarkers in patients with SARS-CoV-2 infection.

BACKGROUND: Lung ultrasound (LUS) has shown to correlate well with the findings obtained by chest computed tomography (CT) in acute-phase COVID-19. Although there is a significant correlation between blood biomarkers and CT radiological findings, a potential correlation between biochemical parameters and LUS images is still unknown. Our purpose was to evaluate whether mortality can be predicted from either of two lung ultrasound scoring systems (LUSS) as well as the potential association between lung lesions visualised by LUS and blood biomarkers. METHODS: We performed a retrospective observational study on 45 patients aged>70 years with SARS-CoV-2 infection who required hospitalisation. LUS was carried out at admission and on day 7, when the clinical course was favourable or earlier in case of worsening. Disease severity was scored by means of LUSS in 8 (LUSS8) and in 12 (LUSS12) quadrants. LUS and blood draw for inflammatory marker analysis were performed at the same time. RESULTS: LUSS8 vs LUSS12 predicted mortality in 93.3% vs 91.1% of the cases; their associated odds ratios (OR) were 1.67 (95% CI 1.20-2.31) and 1.57 (95% CI 1.10-2.23), respectively. The association between biochemical parameters and LUSS scores was significant for ferritin; the OR for LUSS12 was 1.005 (95% CI 1.001-1.009) and for LUSS8 1.005 (95% CI 1.0-1.1), using thresholds for both of them. CONCLUSIONS: The prognostic capacity of LUSS12 does not surpass that of LUSS8. There is a correlation between ferritin levels and LUSS.

Assessing cadmium-based quantum dots effect on the gonads of the marine mussel Mytilus galloprovincialis.

This study assesses the sex-specific effects induced by CdTe QDs, on the marine mussel Mytilus galloprovincialis in comparison to its dissolved counterpart. A 14 days exposure to CdTe QDs and dissolved Cd was conducted (10 µg Cd L-1), analysing Cd accumulation, oxidative stress, biotransformation, metallothionein and oxidative damage in the gonads. Both Cd forms caused significant antioxidant alterations, whereby QDs were more pro-oxidant, leading to oxidative damage, being females more affected. Overall, biochemical impairments on gonads of M. galloprovincialis demonstrate that the reproductive toxicity induced by CdTe QDs in mussels are sex-dependent and mediated by oxidative stress and lipid peroxidation. It is crucial to acknowledge how gametes are affected by metal-based nanoparticles, such as Cd-based QDs. As well as understanding the potential changes they may undergo at the cellular level during gametogenesis, embryogenesis and larval development potentially leading to serious impacts on population sustainability and ecosystem health.

Numerical simulation of lateral and transforaminal lumbar interbody fusion, two minimally invasive surgical approaches.

The present study aims to compare spinal stability after two different minimally invasive techniques, the lateral lumbar interbody fusion (LLIF) and the transforaminal lumbar interbody fusion (TLIF) approaches. Two nonlinear three-dimensional finite element (FE) models of the L4-L5 functional spinal unit (FSU) were subjected to the loads that usually act on the lumbar spine. Findings show that the LLIF approach yields better results for torsion load case, due to the larger surface area of the implant. For extension, flexion and lateral bending loads, the TLIF approach presents smaller displacements probably due to the anterior placement of the cage and to the smaller damaged area of the annulus fibrosus.

Minimally invasive transforaminal and anterior lumbar interbody fusion surgery at level L5-S1.

This paper presents a finite element analysis to investigate the biomechanical changes caused by transforaminal (TLIF) and anterior lumbar interbody fusion (ALIF) at the L5-S1 level, applying two different implants: T_PAL (TLIF) and SynFix (ALIF). The main objective is to determine which one is more stable for patients. Numerical simulations of segmental motion show that, in the early postoperative phase, displacements and rotation angles obtained in ALIF are greater than the corresponding ones obtained in TLIF, as well as the principal stress values on the ligaments. So, TLIF performed with T_PAL is more stable than ALIF, especially during the recovery phase.

Dyslipidaemia and other cardiovascular risk factors in relation to manifest cardiovascular disease in patients with chronic obstructive pulmonary disease in the Canary Islands. / Relación entre la dislipidemia y otros factores de riesgo cardiovasculares conocidos con la presencia de enfermedad cardiovascular en pacientes con enfermedad pulmonar obstructiva crónica de las Islas Canarias.

INTRODUCTION: Cardiovascular disease has a negative impact on the vital prognosis of patients with chronic obstructive pulmonary disease (COPD), where dyslipidaemia (DLP) and arterial hypertension (AHT) are considered the most prevalent risk factors. The objective of this study was 1) to assess the relationship between diagnosed DLP and cardiovascular disease in COPD patients and compare it with other known cardiovascular risk factors and 2) to determine the relationship between the different cardiovascular comorbidities and the severity groups according to the GOLD 2017 classification. METHODS: A cross-sectional, observational study was performed in 454 outpatients with COPD during their follow up. We calculated the prevalence of each of the cardiovascular comorbidities and the probability of each of the cardiovascular risk factors to occur jointly with a vascular disease (RRij). RESULTS: A total of 66.7% of the patients had DLP, whereby DLP was related to cerebrovascular accidents (CVA) (RRij 1.36, P=.0054), chronic kidney disease (CKD) (RRij 1.34, P=.00023), and peripheral arterial disease (PAD) (RRij 1.38, P=.00015). AHT was mostly related to CVA (RRij 1.41, P=.0014) and CKD (RRij 1.42, P<.0001). Type 2 diabetes mellitus (T2DM) correlated with PAD (RRij 1.90, P=.0001), heart failure (HF) (RRij 1,74, P=.0002), and CKD (RRij 1.76, P<.0001), and obesity was associated with HF (RRij 1.60, P=.0009) and CKD (RRij 1.54, P=.0001). CONCLUSION: DLP was related to CVA, CKD, and PAD. AHT and T2DM are the conditions that mostly relate to HF and CVA.

Applicability of the COPD-LUCSS-DLCO score for patients with chronic obstructive pulmonary disease: Analysis in standard clinical practice conditions. / Aplicabilidad del score COPD-LUCSS-DLCO en pacientes con enfermedad pulmonar obstructiva crónica: análisis en condiciones de práctica clínica habitual.

INTRODUCTION: The COPD-LUCSS-DLCO score had been validated as a predictive tool capable of identifying patients with chronic obstructive pulmonary disease (COPD) and a high mortality risk associated with lung cancer (LC); however, studies have not been conducted yet on its use in standard clinical practice. The aim of this study was to estimate the COPD-LUCSS-DLCO scores for patients with COPD treated in Pulmonology consultations and to determine the incidence of LC in each of the subgroups. MATERIAL AND METHODS: A retrospective observational study was conducted with a cohort of 159 patients with COPD in Pulmonology outpatient follow-up consultations. We calculated the COPD-LUCSS-DLCO score (0-8) for each patient, with low risk considered at 0-3 points and high risk at ≥3.5 points. We calculated the incidence rate of LC in each of the subgroups. RESULTS: Sixty-two percent of the patients had a high-risk score. We estimated an overall LC rate of 30 per 1000 patients with COPD-year (95% CI: 16-53), 44 per 1000 patients with COPD-year (95% CI: 18-76) among those categorised as high risk and 17 per 1000 patients with COPD-year among those categorised as low risk (95% CI: 4-50). CONCLUSIONS: The use of the COPD-LUCSS-DLCO score in standard clinical practice could help detect patients with a greater risk of developing LC, which could help to better manage cases in an LC screening programme.

Clinical characteristics of COPD patients with early-onset desaturation in the 6-minute walk test.

BACKGROUND: Exercise-induced desaturation in chronic obstructive pulmonary disease (COPD) frequently has prognostic implications. Desaturation within the first minute of the walk 6-minute walk test will probably also occur in daily life activities and translate into hypoxaemic respiratory failure at rest in later years. This study aimed at comparing these patients with those who desaturate after the first minute and determine potential markers. METHODS: We conducted a cross-sectional, retrospective study collecting data on respiratory function tests, cardiovascular comorbidity, body mass index, pack-year index, 6-minute walk test outcomes, BODE index, and Charlson comorbidity index. Patients who desaturated during the first minute of the test were referred to as early desaturators compared to the non-early ones. RESULTS: We observed a higher mean body mass index in early desaturating patients, and an inverse relation as to the body mass index categories <25, 25-29, and ≥30. Early desaturators had a lower FEV1/FVC index. The mean distance walked in the test was shorter in early than in non-early desaturators, and they desaturated more deeply. CONCLUSION: Overweight and obesity, as determined by body mass index, seem to behave like markers for early desaturation. This simple anthropometric measure might indicate point to potential early desaturation in COPD patients.