Changes in human sweat metabolome conditioned by severity of obstructive sleep apnea and intermittent hypoxemia.

Obstructive sleep apnea (OSA) is a sleep disorder that has been associated with the incidence of other pathologies. Diagnosis is mainly based on the apnea-hypopnea index (AHI) obviating other repercussions such as intermittent hypoxemia, which has been found to be associated to cardiovascular complications. Blood-based samples and urine have been the most utilised biofluids in metabolomics studies related to OSA, while sweat could be an alternative due to its non-invasive and accessible sampling, its reduced complexity, and comparability with other biofluids. Therefore, this research aimed to evaluate metabolic overnight changes in sweat collected from patients with OSA classified according to the AHI and oxygen desaturation index (ODI), looking for potential cardiovascular repercussions. Pre- and post-sleeping sweat samples from all individuals (n = 61) were analysed by gas chromatography coupled to high-resolution mass spectrometry after appropriate sample preparation to detect as many metabolites as possible. Permanent significant alterations in the sweat were reported for pyruvate, serine, lactose, and hydroxybutyrate. The most relevant overnight metabolic alterations in sweat were reported for lactose, succinate, urea, and oxoproline, which presented significantly different effects on factors such as the AHI and ODI for OSA severity classification. Overall metabolic alterations mainly affected energy production-related processes, nitrogen metabolism, and oxidative stress. In conclusion, this research demonstrated the applicability of sweat for evaluation of OSA diagnosis and severity supported by the detected metabolic changes during sleep.

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Retinal and Choroidal Effects of Continuous Positive Airway Pressure as Treatment for Sleep Apnea: Results at 12 Months.

BACKGROUND: To determine the impacts of continuous positive airway pressure (CPAP) treatment on retinal and choroidal thickness measurement in individuals with obstructive sleep apnea (OSA). METHODS: Participants were 28 patients with OSA treated with CPAP who 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 an indication for CPAP. Participants underwent a full ophthalmologic examination including standard automated perimetry (SAP) and optical coherence tomography (OCT) at the levels peripapillary, macular, and choroidal before CPAP onset, and after three and twelve months of CPAP. The data compared before and after treatment were intraocular pressure, SAP, and the thicknesses peripapillary retinal nerve fiber layer (pRNFL), total retinal (TR), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), photoreceptor layer (PL), and choroidal. RESULTS: After 3 months of CPAP, we observed thickening of the pRNFL (in 5/6 subfields) (p < 0.004) and TR (in 5/9 subfields) (p < 0.010). At 12 months, thickening persisted in these layers, this time affecting 2/6 and 2/9 subfields, respectively (p < 0.012 and p < 0.001, respectively). Choroidal thinning was observed at the temporal level at both 3 and 12 months compared to measurements before starting CPAP treatment (p = 0.014 and p = 0.038, respectively). SAP remained unchanged. Intraocular pressure was higher at 12 months than at 3 months (p = 0.001). CONCLUSIONS: 12 months of CPAP avoids retinal thinning and normalizes choroidal thickness in OSA patients.

diaPASEF Proteomics and Feature Selection for the Description of Sputum Proteome Profiles in a Cohort of Different Subtypes of Lung Cancer Patients and Controls.

The high mortality, the presence of an initial asymptomatic stage and the fact that diagnosis in early stages reduces mortality justify the implementation of screening programs in the populations at risk of lung cancer. It is imperative to develop less aggressive methods that can complement existing diagnosis technologies. In this study, we aimed to identify lung cancer protein biomarkers and pathways affected in sputum samples, using the recently developed diaPASEF mass spectrometry (MS) acquisition mode. The sputum proteome of lung cancer cases and controls was analyzed through nano-HPLC-MS using the diaPASEF mode. For functional analysis, the results from differential expression analysis were further analyzed in the STRING platform, and feature selection was performed using sparse partial least squares discriminant analysis (sPLS-DA). Our results showed an activation of inflammation, with an alteration of pathways and processes related to acute-phase, complement, and immune responses. The resulting sPLS-DA model separated between case and control groups with high levels of sensitivity and specificity. In conclusion, we showed how new-generation proteomics can be used to detect potential biomarkers in sputum samples, and ultimately to discriminate patients from controls and even to help to differentiate between different cancer subtypes.

Association between sleep-disordered breathing and prostate cancer.

BACKGROUND: Sleep-disordered breathing (SDB) has been associated with a greater aggressiveness of melanoma tumors, but the association with other cancers is unknown. This study investigates the relationship between the severity of SDB and the aggressiveness of prostate cancer (PC). METHODS: 165 patients under 66 years consecutively diagnosed with PC in three University Hospitals underwent a home respiratory polygraphy. SDB severity was assessed by means of the apnea-hypopnea index (AHI) as well as several oximetric parameters. The primary marker of the aggressiveness of PC was the Gleason score, while secondary markers included the tumor stage and metastatic spreading. RESULTS: The patients had a median (P 25-75) age of 60 (56-63) years, AHI of 13.3 (5.7-25.8), and 4% oxygen desaturation index of 8.7 (2.9-17.8). The prevalence of an AHI≥5 and AHI≥15 was 78.2% and 46.7%, respectively. The median AHI was similar in patients with Gleason 6 and > 6 [13.7 (5.6-28.7) vs 12.2 (5.7-23.2), p = 0.44], tumor stage I-II and III-IV [13.5 (5.3-26.5) vs 11.7 (7.8-21.1), p = 0.67], and presence or absence of metastasis [14.2 (9.6-31.8) vs 13.3 (5.2-24.6), p = 0.46]. The prevalence of an AHI≥5 and AHI≥15 was similar in patients with Gleason 6 and > 6 (79.2% vs 77.2%; p = 0.85, and 49.3% vs 44.33%; p = 0.53, respectively). These results did not change when different oximetric variables were analyzed instead of the AHI. CONCLUSIONS: Despite the high prevalence of SDB in patients with PC, our results do not support any association between the severity of SDB and PC aggressiveness.

Elevated levels of serum CDCP1 in individuals recovering from severe COVID-19 disease.

BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.

Pulmonary long-term consequences of COVID-19 infections after hospital discharge.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) survivors are reporting residual abnormalities after discharge from hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. This study aimed to describe lung function in patients recovering from COVID-19 hospitalization and to identify biomarkers in serum and induced sputum samples from these patients. METHODS: Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalization. Patients' epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardized 6-minute walk test (6MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. RESULTS: A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% of patients (47/100). CT was normal in 48% of patients (48/100). Lung function was normal forced expiratory volume in one second (FEV1) ≥80%, forced vital capacity (FVC) ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide (DLCO) ≥80% in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p < 0.0001) and a lower serum lactate dehydrogenase level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 cases during hospital stay. CONCLUSIONS: A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases.

Clinical Utility of microRNAs in Exhaled Breath Condensate as Biomarkers for Lung Cancer.

This study represents a novel proof of concept of the clinical utility of miRNAs from exhaled breath condensate (EBC) as biomarkers of lung cancer (LC). Genome-wide miRNA profiling and machine learning analysis were performed on EBC from 21 healthy volunteers and 21 LC patients. The levels of 12 miRNAs were significantly altered in EBC from LC patients where a specific signature of miR-4507, miR-6777-5p and miR-451a distinguished these patients with high accuracy. Besides, a distinctive miRNA profile between LC adenocarcinoma and squamous cell carcinoma was observed, where a combined panel of miR-4529-3p, miR-8075 and miR-7704 enabling discrimination between them. EBC levels of miR-6777-5p, 6780a-5p and miR-877-5p predicted clinical outcome at 500 days. Two additional miRNA signatures were also associated with other clinical features such as stage and invasion status. Dysregulated EBC miRNAs showed potential target genes related to LC pathogenesis, including CDKN2B, PTEN, TP53, BCL2, KRAS and EGFR. We conclude that EBC miRNAs might allow the identification, stratification and monitorization of LC, which could lead to the development of precision medicine in this and other respiratory diseases.

Usefulness of Home Overnight Pulse Oximetry in Patients with Suspected Sleep-Disordered Breathing.

Methods: Prospective study conducted in a university hospital. Subjects with a clinical suspicion of SAHS were included. All of them underwent home polygraphy and oximetry on the same night. A correlation was made between the apnea-hypopnea index (AHI) and the oximetry variables. The variable with the highest diagnostic value was calculated using the area under the curve (AUC), and the best cut-off point for discriminating between patients with SAHS and severe SAHS was identified. Results: One hundred and four subjects were included; 73 were men (70%); mean age was 52 ± 10.1 years; body mass index was 30 ± 4.1, and AHI = 29 ± 23.2/h. A correlation was observed between the AHI and oximetry variables, particularly ODI3 (r = 0.850; P < 0.001) and ODI4 (r = 0.912; P < 0.001). For an AHI ≥ 10/h, the ODI3 had an AUC = 0.941 (95% confidence interval (CI) = 0.899-0.982) and the ODI4, an AUC = 0.984 (95% CI = 0.964-1), with the ODI4 having the best cut-off point (5.4/h). Similarly, for an AHI ≥ 30/h, the ODI4 had an AUC = 0.922 (95% CI = 0.859-0.986), with the best cut-off point being 10.5/h. Conclusion: Nocturnal oximetry is useful for diagnosing and evaluating the severity of SAHS. The ODI4 variable was most closely correlated with AHI for both diagnosis.

Effect of a Graduated Walking Program on the Severity of Obstructive Sleep Apnea Syndrome. A Randomized Clinical Trial.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disease. The objective of this research was to determine the effectiveness of a graduated walking program in reducing the apnea-hypopnea index number in patients with obstructive sleep apnea syndrome (OSAS). METHODS: A randomized controlled clinical trial with a two-arm parallel in three tertiary hospitals was carried out with seventy sedentary patients with moderate to severe OSAS. Twenty-nine subjects in each arm were analyzed by protocol. The control group received usual care, while usual care and an exercise program based on progressive walks without direct supervision for 6 months were offered to the intervention group. RESULTS: The apnea-hypopnea index decreased by six points in the intervention group, and improvements in oxygen desaturation index, total cholesterol, and Low-Density Lipoprotein of Cholesterol (LDL-c) were observed. A higher decrease in sleep apnea-hypopnea index (45 ± 20.6 vs. 34 ± 26.3/h; p = 0.002) was found in patients with severe vs. moderate OSAS, as well as in oxygen desaturation index from baseline values (43.3 vs. 34.3/h; p = 0.046). Besides, High-Density Lipoprotein of Cholesterol (HDL-c) values showed a higher increase in the intervention group (45.3 vs. 49.5 mg/dL; p = 0.009) and also, a higher decrease in LDL-c was found in this group (141.2 vs. 127.5 mg/dL; p = 0.038). CONCLUSION: A home physical exercise program is a useful and viable therapeutic measure for the management of OSAS.

Effect of continuous positive airway pressure on inflammatory, antioxidant, and depression biomarkers in women with obstructive sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: The effect of continuous positive airway pressure (CPAP) on mediators of cardiovascular disease and depression in women with obstructive sleep apnea (OSA) is unknown. We aimed to assess the effect of CPAP therapy on a variety of biomarkers of inflammation, antioxidant activity, and depression in women with OSA. METHODS: We conducted a multicenter, randomized controlled trial in 247 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15). Women were randomized to CPAP (n = 120) or conservative treatment (n = 127) for 12 weeks. Changes in tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were assessed. Additional analyses were conducted in subgroups of clinical interest. RESULTS: Women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index 33.5 (29.0-38.3) kg/m2, and AHI 33.3 (22.8-49.3). No differences were found between groups in the baseline levels of the biomarkers. After 12 weeks of follow-up, there were no changes between groups in any of the biomarkers assessed. These results did not change when the analyses were restricted to sleepy women or to those with severe OSA. In women with CPAP use at least 5 hours per night, only TNFα levels decreased compared to the control group (-0.29 ± 1.1 vs -0.06 ± 0.53, intergroup difference -0.23 [95% CI = -0.03 to -0.50]; p = 0.043). CONCLUSIONS: Twelve weeks of CPAP therapy does not improve biomarkers of inflammation, antioxidant activity, or depression compared to conservative treatment in women with moderate-to-severe OSA. TRIAL REGISTRATION: NCT02047071.

Continuous Positive Airway Pressure Treatment Does not Reduce Uric Acid Levels in OSA Women / La presión positiva continua en las vías aéreas no reduce los niveles de ácido úrico en las mujeres con SAOS

Objectives: Although an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA. Methods: We conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n = 151) or conservative treatment (n = 156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence ≥ 4 h/night and those with UA levels ≥ 6 mg/dl. Results: Women had a mean (SD) age of 57.1 (10.1) years, median (first-third quartile) body mass index of 33.7 (29.0-38.5) mg/kg2 and AHI of 32.0 (22.6-48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA ≥ 6 mg/dl. Compared with the control group, the CPAP group did not achieve any reduction in UA levels (non-adjusted intergroup difference -0.03mg/dl, 95%CI -0.20 to 0.13; p = 0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence ≥4 h/night, or the subgroup of women with hyperuricemia. Conclusions: Twelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA

Objetivos: Aunque se ha determinado una asociación entre los niveles de ácido úrico (AU) y el síndrome de apnea obstructiva del sueño (SAOS), el efecto de la presión positiva continua en las vías aéreas (CPAP) en esta medida todavía no está claro. El objetivo fue determinar el efecto de la CPAP en los niveles séricos de AU en pacientes con SAOS. Métodos: Se llevó a cabo un ensayo abierto, aleatorizado, controlado, multicéntrico en 307 mujeres diagnosticadas con SAOS de moderado a grave (índice de apneas-hipopneas [IAH]≥15) en 19 unidades del sueño españolas. Fueron aleatorizadas a recibir CPAP (n=151) o tratamiento conservador (n=156) durante 12 semanas. Los cambios en las medidas de AU sérico se estimaron mediante análisis por intención de tratar. Se llevaron a cabo análisis adicionales en el subgrupo de mujeres con adherencia a CPAP ≥ 4 h/noche y en aquellas con niveles de AU ≥ 6mg/dl. Resultados: La edad media (DE) de las participantes fue 57,1 (10,1) años, la mediana (primer y tercer cuartil) del índice de masa corporal 33,7 (29,0-38,5) mg/kg2 y el IAH 32,0 (22,6-48,5). El nivel medio de AU fue 5,11 (1,26) mg/dl, y 80 (26,1%) participantes tuvieron AU≥6mg/dl. Comparado con el grupo control, el grupo CPAP no consiguió ninguna reducción de los niveles de AU (diferencia intergrupo no ajustada: -0,03 mg/dl; IC 95%: -0,20-0,13; p= 0,702) tras 12 semanas de seguimiento. El análisis no varió cuando se restringió a las mujeres con adherencia a CPAP ≥ 4h/noche o al subgrupo de mujeres con hiperuricemia. Conclusiones: Doce semanas de terapia con CPAP no reducen los niveles de AU en comparación con el tratamiento conservador en mujeres con SAOS de moderado a grave

Continuous Positive Airway Pressure Treatment Does not Reduce Uric Acid Levels in OSA Women.

OBJECTIVES: Although an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA. METHODS: We conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence ≥4h/night and those with UA levels ≥6mg/dl. RESULTS: Women had a mean (SD) age of 57.1 (10.1) years, median (first-third quartile) body mass index of 33.7 (29.0-38.5) mg/kg2 and AHI of 32.0 (22.6-48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA≥6mg/dl. Compared with the control group, the CPAP group did not achieve any reduction in UA levels (non-adjusted intergroup difference -0.03mg/dl, 95%CI -0.20 to 0.13; p=0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence ≥4h/night, or the subgroup of women with hyperuricemia. CONCLUSIONS: Twelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA.

Impact of Positive Pressure Treatment of the Airway on Health-Related Quality of Life in Elderly Patients With Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a chronic illness that increases in prevalence with age. Treatment includes continuous positive airway pressure (CPAP) devices. Studies about the use of CPAP in the elderly are scarce. The main objective of this study is to determine whether CPAP contributes to improvement in health-related quality of life (HRQL) in elderly patients with OSA. METHOD: This was a prospective, pre-/postintervention assessment of a cohort of patients ≥65 years of age with OSA diagnosis by polysomnography who were being treated with CPAP and were physically independent and had good cognitive status. We determined HRQL before and after 3 months of CPAP treatment using the Short Form-36 Health Survey (SF-36, a 36-item, patient-reported survey) and Sleep Apnea Quality of Life Index (SAQLI). The effect of CPAP on daytime sleepiness was assessed with the Epworth Sleepiness Scale (ESS). RESULTS: Of the 103 participants with a mean age of 71.5 ± 4.19 years, 66% were male. After 3 months of therapy, the mean CPAP usage was 6.3 ± 1.41 hr/day. The effectiveness of CPAP in controlling the OSA was demonstrated (mean difference pre- and posttherapy: 34.30 ± 18.52 events/hr, p < .001). Postintervention, the categories of the SF-36 improved meaningfully ( p < .001). Moreover, all categories of SAQLI improved ( p < .001) with the exception of "symptoms" ( p = .073). ESS scores also improved significantly (difference = 5.2 ± 4.47, p < .001) postintervention. CONCLUSION: Therapy with CPAP in elderly patients with OSA helps improve their HRQL and reduces daytime sleepiness.

Effect of continuous positive airway pressure on blood pressure and metabolic profile in women with sleep apnoea.

Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA.A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events·h-1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups.Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (-2.04 mmHg, 95% CI -4.02- -0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (-1.54 mmHg, 95% CI -4.58-1.51; p=0.32) and mean blood pressure (-1.90 mmHg, 95% CI -4.0-0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed.In women with moderate-to-severe OSA, 12 weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment.

Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics.

We explored whether the proteomic analysis of exhaled breath condensate (EBC) may provide biomarkers for noninvasive screening for the early detection of lung cancer (LC). EBC was collected from 192 individuals [49 control (C), 49 risk factor-smoking (S), 46 chronic obstructive pulmonary disease (COPD) and 48 LC]. With the use of liquid chromatography and tandem mass spectrometry, 348 different proteins with a different pattern among the four groups were identified in EBC samples. Significantly more proteins were identified in the EBC from LC compared with other groups (C: 12.4 ± 1.3; S: 15.3 ± 1; COPD: 14 ± 1.6; LC: 24.2 ± 3.6; P = 0.0001). Furthermore, the average number of proteins identified per sample was significantly higher in LC patients, and receiver operating characteristic curve (ROC) analysis showed an area under the curve of 0.8, indicating diagnostic value. Proteins frequently detected in EBC, such as dermcidin and hornerin, along with others much less frequently detected, such as hemoglobin and histones, were identified. Cytokeratins (KRTs) were the most abundant proteins in EBC samples, and levels of KRT6A, KRT6B, and KRT6C isoforms were significantly higher in samples from LC patients (P = 0.0031, 0.0011, and 0.0009, respectively). Moreover, the amount of most KRTs in EBC samples from LC patients showed a significant positive correlation with tumor size. Finally, we used a random forest algorithm to generate a robust model using EBC protein data for the diagnosis of patients with LC where the area under the ROC curve obtained indicated a good classification (82%). Thus this study demonstrates that the proteomic analysis of EBC samples is an appropriated approach to develop biomarkers for the diagnosis of lung cancer.

Continuous Positive Airway Pressure Improves Quality of Life in Women with Obstructive Sleep Apnea. A Randomized Controlled Trial.

RATIONALE: Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed. OBJECTIVES: To investigate the effect of CPAP on QoL in women with moderate to severe OSA. METHODS: We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, ≥15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables. MEASUREMENTS AND MAIN RESULTS: The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P < 0.001 for all domains), daytime sleepiness (-2.92; P < 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003). CONCLUSIONS: In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071).

Human sweat metabolomics for lung cancer screening.

Sweat is one of the less employed biofluids for discovery of markers in spite of its increased application in medicine for detection of drugs or for diagnostic of cystic fibrosis. In this research, human sweat was used as clinical sample to develop a screening tool for lung cancer, which is the carcinogenic disease with the highest mortality rate owing to the advanced stage at which it is usually detected. In this context, a method based on the metabolite analysis of sweat to discriminate between patients with lung cancer versus smokers as control individuals is proposed. The capability of the metabolites identified in sweat to discriminate between both groups of individuals was studied and, among them, a trisaccharide phosphate presented the best independent performance in terms of the specificity/sensitivity pair (80 and 72.7%, respectively). Additionally, two panels of metabolites were configured using the PanelomiX tool as an attempt to reduce false negatives (at least 80% specificity) and false positives (at least 80% sensitivity). The first panel (80% specificity and 69% sensitivity) was composed by suberic acid, a tetrahexose, and a trihexose, while the second panel (69% specificity and 80% sensitivity) included nonanedioic acid, a trihexose, and the monoglyceride MG(22:2). Thus, the combination of the five metabolites led to a single panel providing 80% specificity and 79% sensitivity, reducing the false positive and negative rates to almost 20%. The method was validated by estimation of within-day and between-days variability of the quantitative analysis of the five metabolites.