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.

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.

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.

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.

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.

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.

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.

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.

Relationship of oxidative stress and endothelial dysfunction in sleep apnoea.

The aim of the present study was to evaluate ischaemic reactive hyperaemia (IRH) in obstructive sleep apnoea (OSA) and its relationship with oxidative stress. We studied 69 consecutive patients referred to our Sleep Unit (Reina Sofia University Hospital, Cordoba, Spain). Patients with chronic diseases or those taking medication were excluded. IRH was assessed before and after polysomnography. Morning IRH and oxidative stress markers were compared between patients with (apnoea-hypopnoea index (AHI) ≥ 5) and without (AHI < 5) OSA. Measurements were repeated in 25 severe OSA patients after continuous positive airway pressure (CPAP) therapy. We included 46 OSA patients (mean ± sd AHI 49 ± 32.1) and 23 non-OSA subjects (AHI 3 ± 0.9). The OSA patients showed a significant worsening of morning IRH, and a significant increase in malondialdehyde and 8-hydroxydeoxyguanosine levels. Only the oxygen desaturation index independently explained morning IRH, while malondialdehyde levels showed a weak effect on IRH. In severe OSA patients, IRH improved significantly after CPAP treatment, as did malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyl levels. In OSA patients, endothelial dysfunction and oxidative stress were observed, and IRH worsened after sleep. The increase in oxidative stress was not associated with IRH, while intermittent hypoxia was strongly associated with IRH. In severe OSA patients, CPAP treatment improved oxidative stress and endothelial function.

Sleep disorders are underdiagnosed in patients on maintenance hemodialysis.

BACKGROUND: Sleep apnea-hypopnea syndrome (SAHS) is a cardiovascular risk factor. The aim of this study was to evaluate sleep disorders using polysomnography on a non-selected population of patients on maintenance hemodialysis. METHODS: Overnight polysomnography was performed on 32 hemodialysis patients (24 men/8 women, 54 +/- 16 years), and on 19 healthy subjects of similar age, sex and body mass index who were used as controls. RESULTS: In hemodialysis patients, the most frequent sleep disorder was SAHS in 44% (14/32), followed by insomnia in 41% (13/32). Compared to healthy controls, patients on hemodialysis showed less slow-wave sleep and rapid eye movement sleep (23 vs. 36%, p = 0.001), less sleep efficiency (71 vs. 87%, p = 0.0079) and a higher periodic limb movement index (39.7 vs. 9.1; p = 0.003). An increase in apnea-hypopnea index (18.9 vs. 4.3; p = 0.007) and dips in the SaO(2) (> or =4%) per hour of sleep (22.6 vs. 6.4; p = 0.021) were also significantly greater in hemodialysis patients than controls. 72% of the cases of SAHS were diagnosed solely by means of polysomnography. CONCLUSIONS: The patients on hemodialysis showed poor sleep quality with a significant increase in the apnea-hypopnea index and in the number of dips in SaO(2). SAHS was underdiagnosed in a large percentage of the hemodialysis patients.

[Value of pulse oxymetry for the follow-up control of domiciliary oxygen therapy]. / Rentabilidad de la pulsioximetría para el control de la oxigenoterapia domiciliaria.

OBJECTIVE: To evaluate long-term domiciliary oxygen therapy (LTOT) in our setting and the utility of pulse oxymetry for follow-up control. PATIENTS AND METHOD: 140 patients were studied. The data on the indication for LTOT and the degree of therapeutic compliance were obtained by means of a clinical interview; spirometry, full blood count, arterial blood gas measurement, and pulse oxymetry were also carried out. RESULTS: 12 (8.6%) patients who fulfilled criteria for provisional oxygen therapy were excluded and 22 (15.7%) due to recent exacerbations. Of the remaining 106 individuals, 67 (63%) were men and 39 (37%) women, and the mean age was 73 +/- 12 years. 54% (57/106) of the patients used the oxygen therapy for at least 15 hours/day. Only 36 (34%) patients fulfilled the indication criteria for LTOT and only 24 (23%) both fulfilled the indication criteria and demonstrated appropriate administration of the LTOT. The oxygen saturation measured by pulse oxymetry (SpO2) showed a good correlation with the partial pressure of oxygen (PaO2) obtained by arterial blood gas measurement (r=0.857 and K=0.937). CONCLUSIONS: In our setting, the follow-up control of LTOT and therapeutic compliance were not optimal. The SpO2 shows a good correlation with the PaO2 and represents a good alternative for the follow-up control of LTOT.

[Lung cancer and paraneoplastic syndromes]. / Cáncer de pulmón y síndromes paraneoplásicos.

Paraneoplastic syndromes (PNS) are a relatively common manifestation of cancer, and in some cases they may be the first symptom. Lung cancer has the highest incidence of paraneoplastic syndrome. This fact is important considering a non explained endocrinological and neurological syndrome, it may facilitate a prompt diagnosis, and in some cases an adequate treatment. PNS evolution seems to be parallel to the subjacent cancer. PNS management requires specific measures, because in some cases, it may compromise the patient life. Neurological and endocrinological PNS associated to lung cancer are revised, and diagnosis and treatment of them are updated.

[Aneurysm of the left subclavian artery: infrequent cause of upper pulmonary mass]. / Aneurisma de la arteria subclavia izquierda: causa infrecuente de masa pulmonar superior.

Subclavian artery aneurysm is an uncommon condition. Usually is arteriosclerotic in origin. Its clinical features are scarce and generally are due to compression of the neighbourhood structures or ischemic, embolic or, less frequently, rupture of it. Diagnosis is performed by an arteriography or a computed tomography scan. Treatment includes the surgical reaction or the embolization. We report the case of a patient with a left subclavian artery aneurysm and review the most important clinical features of this entity.

[Domiciliary oxygen therapy. Study of use in a rural area]. / Oxigenoterapia domiciliaria. Estudio de utilización en un área rural.

OBJECTIVE: To assess use of long-term oxygen therapy (LTOT) in a rural community we conducted a transversal study. METHOD: Data was collected in patients' homes, and based on the total number of patients with LTOT, with reference to indication, follow-up and correct completion; two oximetries were carried out, breathing room air, and after breathing oxygen. Of the 70 patients with LTOT, 7 were considered not eligible, the prevalence was found to be: 179/100,000 inhabitants. Sixteen patients were excluded, 6 with exacerbation, and 10 who were unable to be contacted at their home address. The sample was composed of 45 patients. The most frequent diagnosis was COPD (34/45). Indication of LTOT was carried out in the hospital in 40 (89%) patients, and in the health centre in 5 (11%). RESULTS: In 22 (49%) the treatment could be considered acceptable, and only in 21 (46%), the indication of LTOT was correct. Oxygen was administered at least 15 hours/day in 42% of cases (19/45). Patients with periodical check-ups, maintained better pharmacological treatment, although there were no significant differences in the carrying out of LTOT. Using oximetry, it was shown that in 27 patients the SaO2 was lesser than or equal to 88%, and that in 23 cases (85%) administration of oxygen, corrected the saturation. Only in 11 (24%) the indication criteria and adequate administration of LTOT were carried out, as well as correction of the hypoxemia following administration of oxygen. CONCLUSIONS: The prevalence was found to be very high. The results show this form of treatment as being very badly controlled. In a rural community, the pulse oximetry is useful in the follow-up of TLOT.

[Pneumonia and pleural effusion. Therapeutic management]. / Neumonía y derrame pleural. Manejo terapéutico.

The pleural effusion with pneumonia is a common complication. Early diagnosis and adequate handling are required, being based fundamentally on the characteristics of pleural liquid. Antibiotic therapy and pleural drainage are, in most cases, the main basis for very best outcome. Un specific circumstances administration of intrapleural fibrinolysis is increased, giving up surgery for those difficult cases which are not resolved with the previous treatment. The clinical case and the therapeutical different choices are revised, and finally a guideline that helps to the best management of parapneumonic effusion, is suggested.

[Skin metastases, unusual presentation of lung cancer]. / Metástasis cutáneas, presentación inusual del cáncer de pulmón.

The existence of metastasis by lymphatic or hematogenous dissemination, is a regular fact during the course of bronchogenic carcinoma; they were described in different parts of the organism, those regular parts of metastasis are: suprarenals glands, liver, brain, contralateral lung and bone; however the presentation of cutaneous metastasis as first manifestation of lung cancer is infrequent. We revise the literature and we present two cases, remitted from the Service of Surgery in which the were studied for subcutaneous tumor of new appearance.