Retinal and choroidal thickness measurements in obstructive sleep apnea: impacts of continuous positive airway pressure treatment.

PURPOSE: To examine retinal and choroidal thicknesses in individuals with obstructive sleep apnea (OSA) and determine the impacts of continuous positive airway pressure (CPAP) treatment. METHODS: Prospective follow-up study conducted at a university hospital. 40 patients with OSA, 28 treated with CPAP, and 12 untreated, were enrolled immediately after diagnosis and graded according to the apnea hypopnea index (AHI) determined in an overnight polysomnography. Inclusion criteria were a new diagnosis of OSA and CPAP indicated. Participants underwent a full ophthalmologic examination including optical coherence tomography (OCT) at the peripapillary, macular, and choroidal levels and the same examination 3 months later. Outcome measures were peripapillary retinal nerve fiber layer (RNFL), total retinal (TRT), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), photoreceptor layer (PL), and choroidal thicknesses. RESULTS: At 3 months, RGCL thickness was reduced at the inner nasal macula segment in the no-CPAP group (P = 0.016). In + CPAP, increases were produced in RNFL thickness (5/6 segments) and TRT (7/ 9 segments), while choroidal thinning was observed temporally (P = 0.003). At baseline, positive correlation was detected between choroidal thickness and AHI (r = 0.352, P = 0.005) and between IPL thickness (7/9 segments) and AHI (r = 0.414, P < 0.001). CONCLUSIONS: Initial retinal and choroidal thickening was followed by RGCL thinning over 3 months. In patients receiving CPAP, we observed no thinning of any retinal layer and normalization of choroidal thickness.

Resultados preliminares del impacto del ejercicio físico sobre los trastornos respiratorios durante el sueño y metabolismo de la glucosa. Ensayo clínico aleatorizado / Preliminary results for the impact of physical exercise on sleep-related breathing disorders and glucose metabolism. Randomized clinical trial

OBJETIVO: Valorar en pacientes con síndrome de apnea obstructiva del sueño (SAOS) el efecto del ejercicio sobre la gravedad del mismo y el perfil del metabolismo de la glucosa. Análisis preliminar de los resultados del ensayo clínico. PACIENTES Y MÉTODOS: Ensayo clínico aleatorizado con grupos paralelos. Fueron incluidos 38 sujetos sedentarios con un SAOS moderado o grave, si había rechazo de tratamiento con CPAP. Los pacientes fueron aleatorizados al grupo de intervención (programa aeróbico de ejercicio físico) o a un grupo control (medidas habituales) En ambos grupos la actividad física fue medida mediante un podómetro. El diagnóstico se efectuó mediante poligrafía tras la cual se determinó en ayunas el perfil glucémico. Estas medidas se repitieron tras 6 meses de seguimiento. RESULTADOS: Los enfermos que finalizaron el protocolo, 16 en el grupo intervención y 19 en el grupo control, no mostraron diferencias en las características basales. Tras los 6 meses de evolución se observó en el grupo intervención una disminución en el índice de masa corporal y perímetro de cuello (p <0,05). En el grupo intervención disminuyó el índice de apneas-hipopneas/hora (24,9 vs 19,1; p = 0,244), aunque fue significativamente mayor en el índice de desaturaciones >3% (33,2/h vs 18,7/h, p = 0,044), en las cifras de glucemia (101,5 vs 90 mg/dL; p = 0,002) y con tendencia estadística en la insulinemia (12,55 vs 9,30 μU/mL; p = 0,079)CONCLUSIONES: En pacientes con SAOS moderado-grave un programa de ejercicio aeróbico muestra una mejoría clínicamente relevante en la gravedad del SAOS y un efecto positivo en el metabolismo de la glucosa

OBJECTIVE: To evaluate the effect of exercise on the severity of obstructive sleep apnea syndrome (OSAS) as well as the glucose metabolism profile in patients with OSAS. Preliminary analysis of the results of the clinical trial. PATIENTS AND METHODS: Randomized clinical trial with parallel groups. 38 sedentary subjects with moderate or severe OSAS were included if they had refused CPAP treatment. The patients were randomly assigned to the intervention group (aerobic physical exercise program) or a control group (normal measures). Physical activity was measured with a pedometer in both groups. The diagnosis was made using polygraphy after which the glucose profile was determined while fasting. These measurements were repeated after 6 months of follow-up. RESULTS: Patients who completed the protocol, 16 in the intervention group and 19 in the control group, did not show differences in baseline characteristics. After six months of follow-up, a decrease in body mass index and neck perimeter were observed in the intervention group (p <0.05). The apnea-hypopnea/hour index decreased in the intervention group (24.9 vs 19.1; p = 0.244), although the desaturation index >3% (33.2/h vs 18.7/h, p = 0.044) and blood glucose levels (101.5 vs 90 mg/dL; p = 0.002) were significantly higher and there was a statistical insulinemia trend (12.55 vs 9.30 μU/mL; p = 0.079). CONCLUSIONS: In patients with moderate-severe OSAS, an aerobic exercise program shows a clinically relevant improvement in OSAS severity and a positive effect on glucose metabolism

Recomendaciones para la normalización gradual en la enfermedad COVID-19 en las unidades de trastornos respiratorios del sueño de Andalucía / No disponible

No disponible

Diferencias en los metabolismos de sudor según el estadio diagnóstico en cáncer de pulmón escamoso / Metabolite differences in sweat according to diagnostic stage in squamous-cell lung cancer

Objetivo: determinar si la metabolómica aplicada a una muestra de sudor permite diferenciar la concentración relativa de ciertos metabolitos en pacientes con cáncer de pulmón en estadio inicial (I - II) respecto a estadios avanzados (III - IV). Pacientes y métodos: fueron incluidos 21 pacientes diagnosticados de cáncer escamoso de pulmón en un hospital universitario. Para la inducción del sudor se utilizaron discos de Pilogel(R) y la recolección mediante dispositivo Macroduct(R) conservando la muestra a -80 ºC. Para el análisis metabolómico se utilizó un cromatógrafo de líquidos acoplado a un espectrómetro de masas de alta resolución (LC - QTOF) provisto de fuente de ionización por electroespray. Los datos se procesaron con el software MassHunter Workstation y se realizó análisis de cambio (FC, Fold Change Analysis) para detectar las diferencias de concentración relativa de metabolitos entre los diferentes estadios tumorales. Resultados: se estudiaron 21 muestras de sudor pertenecientes a 9 pacientes en estadio I - II y 12 en estadio III - IV. En una lista preferente de 16 compuestos que incluyeron diversos aminoácidos, azúcares, ácidos carboxílicos y ácidos grasos, no se observaron cambios significativos según la extensión tumoral. El análisis de cambio mostró que una trihexosa (FC: -2,175) fue el compuesto con diferencias significativas de concentración relativa en las muestras de sudor según los dos estadios tumoral comparados. Conclusión: en muestras de sudor de pacientes con carcinoma escamoso de pulmón la huella metabolómica se mantiene relativamente estable con escasas diferencias en la concentración relativa de metabolitos, únicamente se observó un cambio significativo en una trihexosa en estadios de cáncer de pulmón inicial y avanzado

Objective: To determine whether applying metabolomics to a sweat sample allows different metabolite concentrations to be differentiated in patients with early-stage lung cancer (stages I-II) compared to advanced stages (III-IV). Patients and methods: 21 patients diagnosed with squamouscell lung cancer in a university hospital were included. Pilogel(R) discs were used to induce sweat, which was collected using the Macroduct(R) system, storing the samples at -80 ºC. For the metabolomic analysis, a liquid chromatograph was used, attached to a high-resolution mass spectrometer (LC - QTOF) supplied with electrospray ionization. The data was processed using the MassHunter Workstation software and a fold change analysis (FC) was done to detect differences in metabolite concentrations between different tumor stages. Results: 21 sweat samples from 9 stage I-II patients and 12 stage III-IV patients were studied. In a list of 16 compounds that included several amino acids, sugars, carboxylic acids and fatty acids, no significant changes were observed according to tumor extension. The change analysis showed that a trihexose (FC: -2.175) was the compound with significant concentration differences in sweat samples according to the two tumor stages compared. Conclusion: In sweat samples from patients with squamouscell lung cancer, metabolomic markers remain relatively stable with slight differences in metabolite concentrations, only observing a significant change in a trihexose between early and advanced stages of lung cancer

Comparación de compuestos metabólicos en muestras de sudor entre pacientes con enfermedad pulmonar obstructiva crónica y cáncer de pulmón / Sweat sample metabolic compound comparison between patients with chronic obstructive pulmonary disease and lung cancer

Objetivo: Evaluar en pacientes con enfermedad pulmonar obstructiva crónica respecto a pacientes con cáncer epidermoide de pulmón en estadio inicial (CP I-II) si en el metaboloma del sudor existen diferencias en los compuestos. Metodología: Se incluyeron 11 pacientes con EPOC y 9 pacientes con CP I-II. El sudor se recogió siguiendo una técnica estandarizada y la muestra fue congelada a -80ºC hasta el análisis metabolómico, para lo que se utilizó un cromatógrafo de líquidos acoplado a un espectrómetro de masas de alta resolución (LC-QTOF) con ionización por electrospray. Se realizó un análisis de cambio (AC) para detectar las diferencias de concentración relativa de metabolitos entre grupos. Resultados. Las características basales de los sujetos incluidos en los dos grupos fueron similares. En la clínica destaca que un 67% de los enfermos con CP I-II (67%) no manifestaron síntomas atribuibles al tumor. El análisis metabolómico mostró que en el análisis de cambio una tetrahexosa presentó diferencias entre el grupo de enfermos con EPOC y con CP I-II (AC: - 4,021), igual tendencia se observó en un trisacárido fosfato (AC: -1,741) y en un lípido sulfónico (AC: -1,920). Conclusión: En muestras de sudor, el análisis de cambio muestra metabolitos con potencialidad para diferenciar entre pacientes EPOC y con CP I-II. Este resultado puede tener aplicabilidad en el cribado del cáncer de pulmón

Objective: To evaluate whether there are differences in sweat metabolite compounds in patients with chronic obstructive pulmonary disease compared to patients with early-stage squamous cell lung cancer (LC I-II). Methods: 11 patients with COPD and 9 patients with LC I-II were included. Sweat was collected using a standardized technique and the sample was frozen at -80ºC until the metabolic analysis was performed, which used a liquid chromatograph coupled with a high-resolution mass spectrometer (LC-QTOF) with electrospray ionization. A change analysis (CA) was done to detect the differences in the relative concentrations of metabolites between groups. Results: The baseline characteristics of subjects included in the two groups were similar. In the clinical presentation, it is worth noting that 67% of patients with LC I-II (67%) did not show symptoms that could be attributed to the tumor. The metabolic analysis showed that in the change analysis, a tetra-hexose showed differences between the COPD group and LC I-II group (CA: -4.021), the same pattern observed in a phosphate trisaccharide (CA: -1.741) and in a sulphonic lipid (AC: -1.920). Conclusion: In sweat samples, the change analysis shows metabolites with the potential to differ between patients with COPD and those with LC I-II. This result can be applied in lung cancer screening

Exhaled breath condensate to discriminate individuals with different smoking habits by GC-TOF/MS.

Smoking is a crucial factor in respiratory diseases and lung inflammation, which are the reasons for high mortality worldwide. Despite the negative impact that tobacco consumption causes on health, few metabolomics studies have compared the composition of biofluids from smoker and non-smoker individuals. Exhaled breath condensate (EBC) is one of the biofluids less employed for clinical studies despite its non-invasive sampling and the foreseeable relationship between its composition and respiratory diseases. EBC was used in this research as clinical sample to compare three groups of individuals: current smokers (CS), former smokers (FS) and never smokers (NS). Special attention was paid to the cumulative consumption expressed as smoked pack-year. The levels of 12 metabolites found statistically significant among the three groups of individuals were discussed to find an explanation to their altered levels. Significant compounds included monoacylglycerol derivatives, terpenes and other compounds, the presence of which could be associated to the influence of smoking on the qualitative and quantitative composition of the microbiome.

Relación entre las variables observadas en una prueba de marcha de 6 minutos y la desaturación nocturna en pacientes con EPOC / Relationship regarding the variables observed in a 6-minute walking test and desaturation at night in COPD

OBJETIVO: Determinar, en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) las variables que en la prueba de 6 minutos marcha (P6MM) aportan información sobre el grado de desaturación nocturna. METODOLOGÍA: Estudio prospectivo, transversal con muestreo consecutivo. Se incluyeron sujetos ambulatorios, en estabilidad clínica, con una saturación periférica de oxígeno (SapO2 ≥92%) y sin contraindicación para realizar una P6MM. A todos los sujetos se les realizaron dos determinaciones con el mismo pulsioxímetro (Pulsox-300i) durante la P6MM y sueño. Se realizó correlación entre las variables de la P6MM y el porcentaje del tiempo nocturno con SapO2 <90% (T90) y se construyó un modelo de regresión para evaluar la variabilidad del T90. RESULTADOS: Fueron incluidos 47 enfermos, 37 hombres (79%), edad = 61,6 ± 7,5 años, y un FEV1 post-BD = 50 ± 18,3 %. Respecto al T90 nocturno, las variables que mostraron correlación significativa en la P6MM fueron la SapO2 , basal, media y mínima, y el T90 y T88 (SapO2 <88%). El modelo de regresión lineal mostró una R2 ajustada de 0,644; (p <0,001) siendo las variables que se asociaron de forma independiente al T90 nocturno: el IMC (p = 0,049), SapO2 basal (p = 0,001), SapO2 media-P6MM (p = 0,006) y el T88-P6MM (p = 0,048). CONCLUSIONES: La P6MM aporta información relevante sobre el grado de desaturación nocturna. La SapO2 basal, y la SapO2 media y el valor del T88 fueron las variables que en la P6MM mostraron mayor influencia sobre la variabilidad del T90 nocturno

OBJECTIVE: Determine in patients with chronic obstructive pulmonary disease (COPD) those variables that provide information about degree of nocturnal desaturation in the 6-minute walk test (6MWT). METHODS: Prospective, transversal study with consecutive sampling. Outpatients were included in clinical stability, with peripheral oxygen saturation (SapO2 ≥92%) and without contraindication for a 6MWT. In all subjects were performed two determinations with the same pulse oximeter (Pulsox-300i) during the 6MWT and sleep. Was performed correlation between variables 6MWT and percentage nigh time with SapO2<90% (T90) and a regression model were constructed to evaluate the variability of the T90. RESULTS: We included 47 patients, 37 men (79%), age = 61.6 ± 7.5 years, and post-BD FEV1 = 50 ± 18.3%. Regard to T90 nocturnal, the variables that showed significant correlation in 6MWT were SapO2 basal, mean and minimum, and T90 and T88 (SapO2 <88%). The linear regression model showed an adjusted R2 of 0.644 (p< 0.001), and BMI (p = 0.049), baseline SapO2 6MWT (p = 0.001), mean SapO2 (p = 0.006) and T88-6MWT (p = 0.048) were the only variables independently associated to nocturnal T90. CONCLUSIONS: The 6MWT provides relevant information on the level of nocturnal desaturation. The basal SapO2 and mean and the value of T88 were the 6MWT variables that showed the greatest influence on variability nocturnal T90

Efectos del tratamiento con presión positiva continua en la vía aérea sobre las funciones cognitivas en pacientes con apnea del sueño grave / Effects of continuous positive airway pressure treatment on cognitive functions in patients with severe obstructive sleep apnoea

Introducción: El síndrome de apnea-hipopnea del sueño (SAHS) tiene numerosas repercusiones sobre la salud y puede afectar a las funciones neurocognitivas de los pacientes. Objetivo: Investigar las funciones neuropsicológicas que resultan más afectadas por el SAHS, los factores asociados a la gravedad del SAHS relacionados con tales limitaciones y el efecto de la terapia con presión positiva continua en la vía aérea. Pacientes y método: La muestra estuvo compuesta por 60 participantes: 30 pacientes con diagnóstico de SAHS (grupo clínico) y 30 personas sin él (grupo control). La memoria, los procesos intelectuales y la atención fueron analizados por los subtests de la batería neuropsicológica de Luria-DNA (subtest de memoria inmediata, memoria lógica, dibujos temáticos y textos, actividad conceptual y discursiva y control atencional). Resultados: Los pacientes mostraron puntuaciones significativamente inferiores a los controles en la mayoría de las áreas evaluadas. Se encontraron asociaciones de la calidad de sueño subjetiva con la actividad conceptual (r = -0,279; p < 0,05) y con el control atencional (r = -0,392; p < 0,01); de la saturación media de oxígeno con la memoria inmediata (r = 0,296; p < 0,05) y con los dibujos temáticos (r = 0,318; p < 0,05); del índice de apnea-hipopnea con la memoria inmediata (r = -0,303; p < 0,05), con la memoria lógica (r = -0,359; p < 0,01) y con los dibujos temáticos (r = -0,302; p < 0,05) de la muestra total. La presión positiva continua en la vía aérea resultó eficaz solamente en la mejora de la memoria inmediata (p = 0,03) de los pacientes con SAHS. Conclusiones: Los pacientes con SAHS grave mostraron alteraciones atencionales y mnésicas relacionadas con un empeoramiento de la calidad del sueño, con unos peores índices de apnea-hipopnea y saturación media de oxígeno. El tratamiento con presión positiva continua en la vía aérea mejoró el rendimiento en la memoria de los pacientes

Introduction: Obstructive sleep apnoea syndrome (OSAS) has numerous implications for health and can affect neurocognitive functions in patients. Objective: To evaluate the neuropsychological functions most affected by OSAS, the factors associated with OSAS severity that are related to those functional limitations, and the effect of therapy with continuous positive airway pressure. Patients and method; The sample consisted of 60 participants: 30 patients diagnosed with OSAS (clinical group) and 30 people without the disorder (control group). Memory, intellectual processes, and attention were analysed with selected subtests from the Luria-Nebraska neuropsychological battery (immediate memory, logical memory, intellectual processes, and attentional control subtests). Results: Patients obtained significantly lower scores than controls in most of the areas evaluated. Associations were identified between subjective sleep quality and conceptual activity (r = -0.279; P < .05) and attentional control (r = -0.392; P < .01); between oxygen saturation and both immediate memory (r = 0.296; P < .05) and thematic drawings (r = 0.318; P < .05); and between apnoea-hypopnoea index and immediate memory (r = -0.303; P < .05), logical memory (r = -0.359; P < .01), and thematic drawings (r = -0.302; P < .05). Continuous positive airway pressure was shown to be effective (P = .03) only for improving immediate memory in patients with OSAS. Conclusions: Patients with severe OSAS showed memory and attentional limitations, associated with poorer quality of sleep and with worst AHI and SaO2 mean. The CPAP use improved memory of the patients evaluated

Desarrollo y validación de un protocolo para el análisis proteómico de muestras de broncoaspirado de pacientes con adenocarcinoma de pulmón / Development and validation of a protocol for the proteomic analysis of bronchoaspiration samples in patients with lung adenocarcinoma

INTRODUCCIÓN: la identificación de marcadores en el broncoaspirado puede representar un hallazgo relevante, complementario al estudio citohistológico. OBJETIVO: determinar si el procedimiento aplicado es válido para obtener péptidos y proteínas suficientes, normalizar el protocolo y realizar un análisis shotgun por espectrometría de masas de los péptidos resultantes. MATERIAL Y MÉTODOS: se incluyeron 4 muestras de broncoaspirado de pacientes con adenocarcinoma de pulmón, aplicando el siguiente flujo de trabajo (I) recolección del broncoaspirado; (II) purificación de su componente proteica; (III) digestión proteica en solución; y (IV) análisis shotgun por espectrometría de masas de los péptidos resultantes. Para clasificar las proteínas según componente celular, proceso biológico y función molecular, se realizó un análisis Gene Onthology. RESULTADOS: en la muestra de 2,1 ml de broncoaspirado medio por paciente, fijando una tasa de falso descubrimiento (FDR, False Discovery Rate) restrictiva del 1%, se identificaron un número elevado de proteínas, con una media de 625, rango entre 529 a 708, y 6.290 péptidos únicos, rango entre 5.585 a 6.759. La composición proteica de las muestras fue homogénea, sin diferencias en la clasificación en relación a los componentes celulares, procesos biológicos y funciones moleculares. La eficacia de la digestión enzimática fue mayor del 90% en todos los casos, lo que asegura la reproducibilidad de la metodología utilizada. CONCLUSIONES: la metodología desarrollada para el análisis proteómico es altamente eficaz y reproducible, identificando un número elevado de proteínas en el broncoaspirado y permitirá realizar, de manera robusta, un estudio cuantitativo en una muestra amplia de pacientes y grupo control

INTRODUCTION: identifying markers in aspirated bronchial samples could represent a relevant discovery, complementary to cytohistological studies, in patients with lung adenocarcinoma. OBJECTIVE: determine whether the procedure applied is valid to obtain sufficient peptides and proteins to establish a protocol and perform mass spectrometry-based shotgun proteomic analysis for the resulting peptides. Material and METHOD: 4 aspirated bronchial samples were included from patients with pulmonary adenocarcinoma, applying the following work flow (I) recollection of aspirated bronchial samples; (II) purification of its protein component; (III) protein digestion in solution; and (IV) mass spectrometry-based shotgun proteomic analysis for the resulting peptides. To classify proteins based on cellular component, biological process and molecular function, gene ontology analysis was performed. RESULTS: in the 2.1 mlmeanbronchial sample per patient, a 1% restrictive false discovery rate (FDR)was established;an elevated number of proteins were identified, with an average of 625, range between 529 to 708 and 6.290 single peptides, range between 5.585 to 6.759. The proteincomposition of the samples was uniform, without differences in the classification with regards to cellular components, biological processes and molecular functions. The efficacy of enzymatic digestion was greater than 90% in all cases, which guarantees the reproducibility of the methodology used. CONCLUSIONS: themethodology developed for the proteomic analysis is highly effective and reproducible; it identifies a high number of proteins in the bronchial samples and allows us to perform, in a robust manner, a quantitative study in a wide range of patients and control group

Identification of metabolomics panels for potential lung cancer screening by analysis of exhaled breath condensate.

Exhaled breath condensate (EBC) is one of the less employed biofluids when searching for clinical markers, despite its non-invasive sampling and the potential relationship between its composition and respiratory disease phenotypes such as lung cancer. The advanced stage at which lung cancer is usually detected is the main reason for the high mortality rate of this carcinogenic disease. In this preliminary research, EBC was used as clinical sample to develop a screening tool for lung cancer discrimination from two control groups (with and without risk factor). Three panels of metabolites were configured using the PanelomiX tool to minimize false negatives (specificity) and false positives (sensitivity). The combination of five metabolites led to three panels providing a sensitivity above 77.9%, specificity above 67.5% and the area under the curve (AUC) above 77.5% for the three panels. An additional study was developed as a first approach to study the statistical significance of metabolites at different stages of lung cancer.

Metabolomics analysis of exhaled breath condensate for discrimination between lung cancer patients and risk factor individuals.

The search for new clinical tests aimed at diagnosing chronic respiratory diseases is a current research line motivated by the lack of efficient screening tools and the severity of some of these pathologies. Alternative biological samples can open the door to new screening tools. A promising biofluid that is rarely used for diagnostic purposes is exhaled breath condensate (EBC), the composition of which has been inadequately studied. In this research, untargeted analysis of EBC using gas chromatography time-of-flight mass spectrometry has been applied to a cohort of patients with lung cancer (n = 48), risk factor individuals (active smokers and ex-smokers, n = 130) and control healthy individuals (non-smokers without respiratory diseases, n = 61). An identical protocol was applied to the two EBC fractions provided by the sampling device (upper and central airways and distal airway) from each individual, which allowed the compositional differences between the two EBC fractions to be detected. Tentative compounds that contribute to discrimination between the three groups were identified, and a relevant role for lipids such as monoacylglycerols and squalene was found. These results could support the ability of metabolomics to go inside the study of lung cancer.

Discovery of potential protein biomarkers of lung adenocarcinoma in bronchoalveolar lavage fluid by SWATH MS data-independent acquisition and targeted data extraction.

UNLABELLED: Lung cancer currently ranks as the neoplasia with the highest global mortality rate. Although some improvements have been introduced in recent years, new advances in diagnosis are required in order to increase survival rates. New mildly invasive endoscopy-based diagnostic techniques include the collection of bronchoalveolar lavage fluid (BALF), which is discarded after using a portion of the fluid for standard pathological procedures. BALF proteomic analysis can contribute to clinical practice with more sensitive biomarkers, and can complement cytohistological studies by aiding in the diagnosis, prognosis, and subtyping of lung cancer, as well as the monitoring of treatment response. The range of quantitative proteomics methodologies used for biomarker discovery is currently being broadened with the introduction of data-independent acquisition (DIA) analysis-related approaches that address the massive quantitation of the components of a proteome. Here we report for the first time a DIA-based quantitative proteomics study using BALF as the source for the discovery of potential lung cancer biomarkers. The results have been encouraging in terms of the number of identified and quantified proteins. A panel of candidate protein biomarkers for adenocarcinoma in BALF is reported; this points to the activation of the complement network as being strongly over-represented and suggests this pathway as a potential target for lung cancer research. In addition, the results reported for haptoglobin, complement C4-A, and glutathione S-transferase pi are consistent with previous studies, which indicates that these proteins deserve further consideration as potential lung cancer biomarkers in BALF. Our study demonstrates that the analysis of BALF proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS), combining a simple sample pre-treatment and SWATH DIA MS, is a useful method for the discovery of potential lung cancer biomarkers. SIGNIFICANCE: Bronchoalveolar lavage fluid (BALF) analysis can contribute to clinical practice with more sensitive biomarkers, thus complementing cytohistological studies in order to aid in the diagnosis, prognosis, and subtyping of lung cancer, as well as the monitoring of treatment response. Here we report a panel of candidate protein biomarkers for adenocarcinoma in BALF. Forty-four proteins showed a fold-change higher than 3.75 among adenocarcinoma patients compared with controls. This report is the first DIA-based quantitative proteomics study to use bronchoalveolar lavage fluid (BALF) as a matrix for discovering potential biomarkers. The results are encouraging in terms of the number of identified and quantified proteins, demonstrating that the analysis of BALF proteins by a SWATH approach is a useful method for the discovery of potential biomarkers of pulmonary diseases.

Effects of continuous positive airway pressure treatment on cognitive functions in patients with severe obstructive sleep apnoea. / Efectos del tratamiento con presión positiva continua en la vía aérea sobre las funciones cognitivas en pacientes con apnea del sueño grave.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) has numerous implications for health and can affect neurocognitive functions in patients. OBJECTIVE: To evaluate the neuropsychological functions most affected by OSAS, the factors associated with OSAS severity that are related to those functional limitations, and the effect of therapy with continuous positive airway pressure. PATIENTS AND METHOD: The sample consisted of 60 participants: 30 patients diagnosed with OSAS (clinical group) and 30 people without the disorder (control group). Memory, intellectual processes, and attention were analysed with selected subtests from the Luria-Nebraska neuropsychological battery (immediate memory, logical memory, intellectual processes, and attentional control subtests). RESULTS: Patients obtained significantly lower scores than controls in most of the areas evaluated. Associations were identified between subjective sleep quality and conceptual activity (r=-0.279; P<.05) and attentional control (r=-0.392; P<.01); between oxygen saturation and both immediate memory (r=0.296; P<.05) and thematic drawings (r=0.318; P<.05); and between apnoea-hypopnoea index and immediate memory (r=-0.303; P<.05), logical memory (r=-0.359; P<.01), and thematic drawings (r=-0.302; P<.05). Continuous positive airway pressure was shown to be effective (P=.03) only for improving immediate memory in patients with OSAS. CONCLUSIONS: Patients with severe OSAS showed memory and attentional limitations, associated with poorer quality of sleep and with worst AHI and SaO2 mean. The CPAP use improved memory of the patients evaluated.

Efecto del ejercicio sobre la somnolencia y la calidad de vida en pacientes con apneas del sueño sin indicación de tratamiento con CPAP / Effect of exercise for excessive daily sleepiness and quality of life in obstructive sleep apnea patients without CPAP device indication

OBJETIVO: Determinar el efecto del ejercicio sobre la calidad de vida e impacto en actividades cotidianas de la vida de los pacientes con síndrome de apneas-hipopneas del sueño (SAHS) leve. PACIENTES Y MÉTODOS: Ensayo clínico controlado, aleatorizado y de grupos paralelos. Se incluyeron sujetos con un índice de apneas-hipopneas (IAH) < 20 y escasa actividad física. Los sujetos fueron aleatorizados a un grupo, que realizó un programa aeróbico de ejercicio físico, frente a un grupo que realizó las medidas habituales. Después de 24 semanas, se determinaron nuevamente la calidad de vida (cuestionario Euroqol-5D) y el impacto sobre las actividades de la vida cotidiana (cuestionario FOSQ). RESULTADOS: De los 27 pacientes con SAHS leve, no se analizaron 3 sujetos del grupo intervención (23%), ya que no cumplieron el programa de ejercicio, y 1 sujeto del grupo control (7%). Las características basales fueron similares en ambos grupos. Tras el seguimiento, en el grupo control (n = 13) no se encontraron diferencias respecto a los valores basales, mientras que en grupo intervención (n = 10) se observaron cambios significativos en la calidad de vida (movilidad, puntuación total de salud y autovaloración, p < 0,05) y en la puntuación del cuestionario FOSQ (cálculo total, dimensiones de productividad social, actividad, vigilancia e intimidad; p < 0,05), sin cambio significativo en el cuestionario de Epworth. CONCLUSIONES: En pacientes con SAHS leve, un programa de ejercicio aeróbico produce mejoría en la calidad de vida y en el impacto de la somnolencia diurna sobre su vida cotidiana

OBJECTIVE: To determine the effect of exercise in health-related quality of life and how it impacts on daily activities in mild obstructive sleep apnea (OSA) patients. Patients and METHODS: Controlled clinical trial, randomized and parallel groups. Patients with an apnea-hipopnea index (AHI) < 20 and with mild activity were included. Randomly, patients were undertaken to an aerobic program (intervention group) or to an usual therapeutic measures (control group). We analyzed health-related quality of life (Euroqol-5D questionnaire) and the impact on daily activities (FOSQ questionnaire) after 24 weeks. RESULTS: 27 patients were included. 3 patients in the intervention group (23%) with mild OSA were no analyzed because of lack of exercise adherence, while in the control group 1 patient (7%) was lost. Characteristics were similar in both groups. There were no differences in basal statements in the control group (n =13) after the following period. There were stadistical differences in quality of life (mobility, total score and visual anagogic scale score; p < 0.05) and in FOSQ questionnaire score (total score, social outcomes, activity level, vigilance and intimacy and sexual subscales; p < 0.05) in the interventional group (n = 10). No significant change in the Epworth questionnaire was observed. CONCLUSIONS: An aerobic exercise program in patients with mild OSA improves quality of life and produces a positive impact in daytime sleepiness on activities of daily living

Development of a method for metabolomic analysis of human exhaled breath condensate by gas chromatography-mass spectrometry in high resolution mode.

Exhaled breath condensate (EBC) is a promising biofluid scarcely used in clinical analysis despite its non-invasive sampling. The main limitation in the analysis of EBC is the lack of standardized protocols to support validation studies. The aim of the present study was to develop an analytical method for analysis of human EBC by GC-TOF/MS in high resolution mode. Thus, sample preparation strategies as liquid-liquid extraction and solid-phase extraction were compared in terms of extraction coverage. Liquid-liquid extraction resulted to be the most suited sample preparation approach providing an average extraction efficiency of 77% for all compounds in a single extraction. Different normalization approaches were also compared to determine which strategy could be successfully used to obtain a normalized profile with the least variability among replicates of the same sample. Normalization to the total useful mass spectrometry signal (MSTUS) proved to be the most suited strategy for the analysis of EBC from healthy individuals (n = 50) reporting a within-day variability below 7% for the 51 identified compounds and a suited data distribution in terms of percentage of metabolites passing the Skewness and Kurtosis test for normality distribution. The composition of EBC was clearly dominated by the presence of fatty acids and derivatives such as methyl esters and amides, and volatile prenol lipids. Therefore, EBC offers the profile of both volatile and non-volatile components as compared to other similar biofluids such as exhaled breath vapor, which only provides the volatile profile. This human biofluid could be an alternative to others such as serum/plasma, urine or sputum to find potential markers with high value for subsequent development of screening models.

A basic intervention improves CPAP adherence in sleep apnoea patients: a controlled trial.

BACKGROUND: The treatment of choice for sleep apnoea-hypopnoea syndrome (SAHS) is continuous positive airway pressure (CPAP). However, CPAP effectiveness strongly depends on patient adherence to treatment. The aim of this study was to determine the effectiveness of a low-cost, basic intervention on improving CPAP adherence. METHODS: A controlled parallel-group trial. Participants were SAHS patients for whom CPAP treatment was indicated. Those in the intervention group were shown the results of their sleep test and were told the importance of treatment adherence; the control group received neither. Outcomes for both groups were compared at 6 months. The primary outcome assessed was CPAP usage. RESULTS: One hundred fifty-four patients were included in the intervention group and 167 in the control group. At 6 months, the intervention group had 10% more participants with CPAP usage ≥4 h, significantly higher adherence as compared to controls (5 ± 1.8 h vs 4.3 ± 1.7, p = 0.031), mean: 0.7 h/day and fewer discontinuations of CPAP. A multiple linear regression model showed that intervention group and daytime sleepiness were variables independently associated with treatment adherence. CONCLUSIONS: An inexpensive basic intervention involving communication of sleep test results and the importance of CPAP adherence improves adherence to CPAP therapy. In addition, greater daytime sleepiness is associated with higher CPAP adherence.

Estudio metabolómico en el sudor. Aportación diagnóstica en el cáncer de pulmón / Metabolomic study on the sweat. Diagnostic contribution in lung cáncer

OBJETIVOS: detectar si existen compuestos en el sudor con potencialidad diagnóstica en el cáncer de pulmón (CP). MÉTODOS: estudio observacional, de cohortes, realizado en un Hospital Universitario. Los sujetos fueron adscritos a grupo con CP, grupo sin CP y sin factor de riesgo (no fumadores) y grupo sin CP y con factor de riesgo (consumo > 20 paquetes/año). Fueron excluidos sujetos > 80 años, existencia de enfermedad grave de órgano, neoplasia extrapulmonar o tratamiento previo con citostáticos. La muestra de sudor se conservó a -80 ºC. Para su análisis se trasvasó cuantitativamente a viales del automuestreador para extracción en fase sólida y retener los componentes de interés. Tras eliminar la matriz de la muestra, los compuestos se eluyeron al instrumento analítico, utilizando la fase móvil cromatográfica. En esta etapa se aplicó el diseño quimiométrico más adecuado en cada caso. RESULTADOS: se incluyeron 96 sujetos. Con las muestras de sudor de cada uno de los 3 subgrupos se formó un pool, que se inyectó 10 veces consecutivas en el cromatógrafo de líquidos acoplado al espectrómetro de masas en tándem (LC-MS/MS). Se observó discriminación entre los tres subgrupos mediante el análisis por componentes principales del perfil de metabolitos detectado por LC-MS/MS y demostró la capacidad para clasificar los pacientes con CP de los individuos control, con y sin factor de riesgo. CONCLUSIÓN: el estudio del sudor abre un campo de investigación novedoso y con importante aplicabilidad clínica, ya que este modelo podría convertirse en una herramienta diagnóstica no invasiva en el CP

AIMS: to detect the presence of sweat compounds with potential diagnostic of lung cancer (LC). METHODS: observational cohort study in a University Hospital. The participants were assigned in a group with LC, a group without LC and without risk factor (non-smoking) and a group without LC and with risk factor (tobacco consumption > 20 package/year). The subjects > 80 years old, severe lung organ disease, extrapulmonary neoplasia or cytostatic pre-treatment were excluded. The sweat sample was stored at -80ºC. For analysis, it was transferred into autosampler vials for solid phased extraction (SPE) in order to keep the interesting compounds. After removing the sample matrix, the compounds were eluted to the analytical instrument using the chromatographic mobile phase. At this stage, the most suitable chemometric design was applied in each case. RESULTS: the population consisted of 96 subjects. A pool establish by the three subgroups sweat samples was injected ten times and row in the liquid chromatograph coupled to mass spectrometer (LC-MS/MS). In was noticed a discrimination between the three subgroups by analyzing the main compounds in metabolite profile, detected by LC-MS/MS. This proved the ability to distinguish patients with LC from control subjects with and without risk factor. CONCLUSIONS: the sweat study open up a novel research field with an important clinical relevance, because this model could become a non invasive diagnostic tool in the LC

Cifras séricas de alanino aminotransferasa y síndrome de apneas-hipopneas del sueño / Serum levels of alanine aminotransferase and sleep apnea-hypopnea syndrome

OBJETIVO: comparar en pacientes con síndrome de apneas-hipopneas del sueño (SAHS) los valores séricos de alanino-aminotransferasa (ALT) respecto a un grupo sin SAHS. PACIENTES Y MÉTODOS: se estudiaron 69 sujetos remitidos a la unidad del sueño, a los que se les realizó una polisomnografía. Se excluyeron aquellos pacientes con enfermedad crónica, excesiva ingesta de alcohol o medicación hepatotóxica. Los valores séricos de ALT de los pacientes diagnosticados de SAHS (índice de apneas-hipopneas, IAH ≥ 5) se compararon con los de un grupo sin SAHS (IAH < 5). RESULTADOS: se incluyeron 46 pacientes con SAHS (IAH = 49 ± 32,1) y 23 sujetos sin SAHS (IAH = 3 ± 0,9). No se observaron diferencias significativas en edad, género e índice de masa corporal. Los pacientes mostraron un incremento significativo de los valores séricos de ALT respecto al grupo control. En los enfermos con SAHS no se observó correlación entre las cifras de ALT y los parámetros relacionados con la SapO2 nocturna. Al contrario, el valor de la 8-hidroxiguanosina mostró correlación significativa con la ALT (rho = 0,494; P = 0,001) y, en el modelo de regresión lineal multivariante, fue la única variable que se asoció independientemente a las cifras de ALT (p = 0,012).CONCLUSIONES: en pacientes diagnosticados de SAHS, el valor sérico de ALT se encuentra significativamente elevado respecto el grupo control. En nuestro estudio, la hipoxemia intermitente no explica la variabilidad de la ALT, mientras que la 8-hidroxiguanosina puede jugar un papel importante en la elevación de la ALT

OBJECTIVE: to compare alanine aminotransferase (ALT) serum levels in patients with sleep apnea-hypopnea syndrome (SAHS) respect patients without SAHS. PATIENTS AND METHODS: We studied 69 patients referred to our Sleep Unit. Sleep was studied using overnight polysomnography. Patients with hepatotoxic medication, chronic diseases or excessive alcohol consumption were excluded. Serum ALT levels in patients with SAHS, apnea-hypopnea index (AHI) ≥ 5, were compared with ALT levels from subjects without SAHS (AHI < 5). RESULTS: we included 46 patients with SAHS (AHI 49 ± 32.1) and 23 subjects without SAHS (AHI 3 ± 0.9). No significative differences in age, gender and body mass index were observed. Serum ALT levels increased significantly in SAHS patients respect control group. There were not correlation between ALT levels and nocturnal SpO2 parameters. Nevertheless, 8-hydroxyguanosine values showed significative correlation with ALT levels (rho = 0.494; P = 0.001). In multivariate lineal regression, the 8-hydroxyguanosine was the only parameter that independently associated to ALT values (p = 0.012). CONCLUSIONS: in patients with SAHS, serum ALT level is significantly increased respect control group. In our study, intermittent hypoxemia doesn't explain the variability of ALT, while 8-hydroxyguanosine could play an important role at ALT elevation

Optimization study for metabolomics analysis of human sweat by liquid chromatography-tandem mass spectrometry in high resolution mode.

Sweat has recently gained popularity as a potential tool for diagnostics and biomarker monitoring as it is a non-invasive biofluid the composition of which could be modified by certain pathologies, as is the case with cystic fibrosis, which increases chloride levels in sweat. The aim of the present study was to develop an analytical method for analysis of human sweat by liquid chromatography-mass spectrometry (LC-Q-TOF MS/MS) in high resolution mode. Thus, different sample preparation strategies and different chromatographic modes (HILIC and C18 reverse modes) were compared to check their effect on the profile of sweat metabolites. Forty-one compounds were identified by the MS/MS information obtained with a mass tolerance window below 4 ppm. Amino acids, dicarboxylic acids and other interesting metabolites such as inosine, choline, uric acid and tyramine were identified. Among the tested protocols, direct analysis after dilution was a suited option to obtain a representative snapshot of sweat metabolome. In addition, sample clean up by C18 SpinColumn SPE cartridges improved the sensitivity of most identified compounds and reduced the number of interferents. As most of the identified metabolites are involved in key biochemical pathways, this study opens new possibilities to the use of sweat as a source of metabolite biomarkers of specific disorders.

Cardiopatía isquémica y frecuencia del síndrome de apneas-hipopneas durante el sueño / Ischemic cardiac disease and frequency of sleep apnea syndrome

OBJETIVOS: establecer la frecuencia del síndrome de apneas-hipopneas del sueño (SAHS) en pacientes con cardiopatía isquémica y valorar si la sintomatología puede ayudar a sospechar el diagnóstico en esta población. PACIENTES Y MÉTODOS: los pacientes elegibles fueron remitidos consecutivamente, en estabilidad clínica, a la Unidad de Trastornos Respiratorios del Sueño tras un ingreso hospitalario por cardiopatía isquémica. A todos se les realizó una historia clínica y exploración física, con especial atención a los hábitos y características del sueño, síntomas nocturnos/diurnos, y comorbilidad. El diagnóstico de SAHS fue considerado si el sujeto presentó un IAH ≥ 10 /hora, registrado por poligrafía respiratoria. RESULTADOS: fueron incluidos 55 enfermos, realizándose el diagnóstico de SAHS en 29 (53%), de los que sólo 1 había sido diagnosticado previamente. Respecto al grupo control, los pacientes con SAHS presentaron mayor porcentaje de factores de riesgo vascular, incluyendo hipertensión, diabetes mellitus y dislipemia, aunque sin alcanzar significación estadística. La sintomatología en ambos grupos fue similar, salvo las apneas observadas durante el sueño, que fueron significativamente más abundantes en el grupo con SAHS (p = 0,006).CONCLUSIONES: en pacientes con cardiopatía isquémica, el porcentaje con SAHS es mayor que el descrito en la población general, y la mayoría de los casos no están diagnosticados. El cuadro clínico es inespecífico, y sólo las apneas observadas son síntoma de que puede aumentar la sospecha diagnóstica de SAHS

OBJECTIVES: establish the percentage of sleep apnea-hypopnea syndrome (SAHS) in patients with ischemic heart disease and assess whether the symptoms can help to suspect the diagnosis in this population. PATIENTS AND METHODS: elegible patients were consecutively referred in clinical stability after an admission for ischemic heart disease to the unit of sleep-disorder breathing. All patients underwent a medical history and physical examination with special attention to the habits and characteristics of sleep, nighttime and daytime symptoms, and comorbidity. The diagnosis of SAHS was considered if the subject had an AHI ≥ 10/ h, by using a respiratory poligraphy. RESULTS: we included 55 patients, performing diagnosis of SAHS in 29 (53%) of them. Only one patient was previously diagnosed. Respect to control group, patients with SAHS had a higher percentage of vascular risk factors, including hyper-tension, diabetes mellitus and dyslipidemia, although not statistically significant (p > 0,05). The symptoms in both groups was similar, except witnessed apneas during sleep was signifiantly higher in the SAHS group (p = 0,006).CONCLUSIONS: in patients with ischemic heart disease the per-centage of SAHS is higher than in the general population, most of the patients are not previously diagnosed. The semiology is nonspecific and the witnessed apneas are the only symptom that can increase the diagnostic suspicion