Sleep biosignature of Type 2 diabetes: a case-control study.

AIM: To determine whether or not the sleep disturbances associated with Type 2 diabetes affect the structure of sleep. METHODS: We designed a case-control study in 76 patients with Type 2 diabetes and 76 control subjects without Type 2 diabetes, matched by age, gender, BMI and waist and neck circumferences. A subgroup of 32 patients with Type 2 diabetes was also matched with 64 control subjects without Type 2 diabetes according to apnoea-hypopnoea index score. Examination included an overnight full polysomnography. RESULTS: No differences in the percentage of time spent in either rapid eye movement or non-rapid eye movement sleep were observed between groups; however, patients with Type 2 diabetes had more microarousal events during sleep than control subjects [41.4 (total range 4.0-104.4) vs 20.7 (total range 1.3-94.5) events/h; P < 0.001]. These differences were mainly observed during the non-rapid eye movement sleep [7.4 (total range 0-107.2) vs 0.2 (total range 0-65.2) events/h; P < 0.001]. In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation ≤90%, were significantly greater during the rapid eye movement sleep in patients with Type 2 diabetes [20.3 (total range 0-99.2) vs. 10.5 (total range 0-94.0)%; P = 0.047]. This pattern was maintained in the subgroup of patients matched by apnoea-hypopnaea index. Finally, stepwise regression analyses showed that apnoea-hypopnoea index, the presence of Type 2 diabetes and fasting plasma glucose value were independently associated with the number of microarousals (R2 =0.667). CONCLUSIONS: Type 2 diabetes is associated with an altered sleep structure, with different effects according to rapid eye movement (increase in nocturnal hypoxia) or non-rapid eye movement (increase in sleep fragmentation) sleep.

Strokes and their relationship with sleep and sleep disorders.

INTRODUCTION: In the current population, strokes are one of the most important causes of morbidity and mortality, to which new risk factors are increasingly being attributed. Of late, there is increased interest in the relationship between sleep disorders and strokes as regards risk and prognosis. DEVELOPMENT: This article presents the changes in sleep architecture and brain activity in stroke patients, as well as the interaction between stroke and sleep disorders, including those which may also influence the outcome and recovery from strokes. The different treatments discussed in the literature are also reviewed, as correct treatment of such sleep disorders may not only improve quality of life and reduce after-effects, but can also increase life expectancy. CONCLUSIONS: Sleep disorders are becoming increasingly associated with stroke. In addition to being a risk factor, they can also interfere in the outcome and recovery of stroke patients. This article aims to present an exhaustive and current review on strokes and their relationship with sleep alterations and sleep disorders.

TNF-α system and lung function impairment in obesity.

A potential interaction between pulmonary function, abnormal adipose tissue activity, and systemic inflammation has been suggested. This study explores the relationship between circulating soluble TNF-α receptors (sTNF-R1 and sTNF-R2) and respiratory function parameters in obese subjects. Thirty-one non-diabetic morbidly obese women with a history of non-smoking and without prior cardiovascular or respiratory disease were prospectively recruited in the outpatient Obesity Unit of a referral center. Pulmonary function test included a forced spirometry, static pulmonary volume measurements, non-attended respiratory polygraphy, and arterial gas blood sampling. Circulating levels of sTNFR-R1, sTNF-R2, interleukine 6 and adiponectin were determined using ELISA. Statistical analysis included a multivariate regression analysis taking into account the potential confounders. sTNF-R1 positively correlated with BMI (r=0.571, p=0.001) and arterial carbon dioxide pressure (PaCO(2), r=0.381, p=0.038), but negatively with forced expiratory volume in 1s (FEV(1), r=-0.437, p=0.012), maximum midexpiratory flow (FEF(25-75), r=-0.370, p=0.040) and forced vital capacity (FVC, r=-0.483, p=0.005). However, no correlation between sTNF-R2 and BMI and either pulmonary function tests or arterial blood samples was observed. Multiple linear regression analysis showed that sTNF-R1 independently predicted FEV(1) (beta=-0.437, p=0.012) and FVC (beta=-0.483, p=0.005). Thus, circulating levels of sTNF-R1, but not sTNF-R2, are related to reduced lung volumes and airflow limitation in morbidly obese patients prior to the development of a clinically recognized respiratory disease. Therefore, studies addressed to evaluating the potential beneficial effect of anti-TNF-α agents on pulmonary function tests in obese subjects seem warranted.

Type 2 diabetes impairs pulmonary function in morbidly obese women: a case-control study.

AIMS/HYPOTHESIS: To determine whether the presence of type 2 diabetes and the degree of metabolic control are related to reduced pulmonary function in obese individuals. METHODS: Seventy-five morbidly obese women (25 with type 2 diabetes [cases]--and 50 without diabetes [controls]) with a history of non-smoking and without prior cardiovascular or respiratory disease were prospective recruited for a case-control study in the outpatient obesity unit of a referral centre. Both groups were closely matched by age, BMI and waist circumference. Pulmonary function test included forced spirometry and static pulmonary volume measurements. RESULTS: Type 2 diabetic patients showed lower forced expiratory volume at 1 s (FEV1) (mean difference -11.6% of predicted [95% CI -20.4 to -2.8]; p = 0.011), and FEV1/forced vital capacity (FEV1/FVC) ratio (mean difference -4.4% [95% CI -8.1 to -0.7]; p = 0.049), but a greater residual volume (RV) (mean difference 19.5% of predicted [95% CI 10.8-28.3]; p < 0.001). In addition, an obstructive ventilatory pattern was more frequent in diabetic patients. Significant negative correlations between FEV1 and fasting glucose, HbA1c and HOMA insulin resistance (HOMA-IR) were detected. By contrast, RV was positively correlated with fasting glucose, HbA1c and HOMA-IR. Multiple linear regression analyses showed that fasting glucose and HbA1c independently predicted FEV1 and RV. CONCLUSIONS/INTERPRETATION: The presence of diabetes and the degree of glycaemic control are related to respiratory function impairment in morbidly obese women. Therefore, the impact of type 2 diabetes on pulmonary function should be taken into consideration by those providing care for obese people.

Accuracy and reliability of pulse oximetry at different arterial carbon dioxide pressure levels.

The present study aimed to assess whether arterial carbon dioxide pressure (Pa,CO(2)) has an impact on agreement between oxygen saturation measured with pulse oximetry (Sp,O(2)) or arterial blood gas co-oximetry (Sa,O(2)). Sa,O(2) and Sp,O(2) determinations were obtained simultaneously from 846 patients under assessment for long-term home oxygen therapy in a specialised outpatient clinic. Both measurements were taken with patients seated and breathing room air. Agreement between Sa,O(2) and Sp,O(2) results was analysed by the Bland-Altman method and the Lin concordance coefficient. In addition, potential interactions of arterial oxygen tension (Pa,O(2)) or Pa,CO(2) on agreement were analysed by adjusted multivariate analysis. Upon comparison of Sa,O(2) and Sp,O(2) results, the Bland-Altman technique yielded a bias (95% confidence interval (CI)) of -1.24 (-6.86-4.38) and -1.32 (-7.78-5.15) when Pa,CO(2) >48 mmHg (6.39 kPa) or Pa,O(2) <54 mmHg (7.20 kPa), respectively. Estimate by Lin's coefficient (95% CI) in these cases was 0.88 (0.85-0.90) and 0.81 (0.77-0.85). Adjusted multivariate analysis, performed to assess the impact of pH, Pa,O(2), Pa,CO(2) and bicarbonate on bias, showed that Pa,O(2), Pa,CO(2) and their interaction terms were the most important predictors of the bias (standardised estimates of -0.54, -0.94, and 0.85, respectively). The effect of pH, although statistically significant, was small, and bicarbonate had no significant effect. Arterial carbon dioxide pressure status can contribute to impaired agreement between arterial oxygen saturation and arterial oxygen saturation measured with pulse oximetry, particularly in patients with hypercapnia.

Intermittent hypoxia is an independent marker of poorer glycaemic control in patients with uncontrolled type 2 diabetes.

AIM: This study investigated the association between intermittent hypoxia and glycaemic control in patients with uncontrolled type 2 diabetes (T2D) not treated for sleep apnoea. METHODS: This was a single-centre cross-sectional study of stable patients with T2D and HbA1c ≥7% (53 mmol/mol). Patients underwent overnight pulse oximetry and, if intermittent hypoxia-defined by a 4% oxyhaemoglobin desaturation index ≥15-was observed, respiratory polygraphy was performed. All participants completed the Pittsburgh Sleep Questionnaire and Hospital Anxiety and Depression Scale. The association between intermittent hypoxia and poorer glycaemic control (defined by an HbA1c level above the median of 8.5%) was estimated by multivariate logistic regression analysis. RESULTS: Out of 145 patients studied, 54 (37.2%) had intermittent hypoxia (with sleep apnoea confirmed in 53). Patients with intermittent hypoxia had 0.7% (7.7 mmol/mol) higher median HbA1c levels than patients without intermittent hypoxia (P=0.001). Intermittent hypoxia was associated with poorer glycaemic control after adjusting for obesity, age at onset and duration of diabetes, insulin requirement, sleep quality and depressive mood (OR: 2.31, 95% CI: 1.06-5.04, model adjusted for body mass index; OR: 2.46, 95% CI: 1.13-5.34, model adjusted for waist-to-height ratio). CONCLUSION: Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

Self-reported sleepiness while driving as a risk factor for traffic accidents in patients with obstructive sleep apnoea syndrome and in non-apnoeic snorers.

The obstructive sleep apnoea syndrome (OSAS) is a condition causing daytime sleepiness and has been related to an increased risk for traffic accidents. However, the evidence linking severity of OSAS to a higher rate of automobile crashes is based on limited data. The aims of this study were to study the traffic accident rate in the last 5 years in patients referred to our sleep clinic because of clinical suspicion of OSAS and to analyse variables related to an increased risk for traffic accidents. A series of 189 consecutive patients with a driving license referred for a sleep study because of OSAS clinical suspicion and a control group (CG) of 40 hospital staff workers who denied snoring, matched for age and sex with the study population, were studied. Patients underwent a full-night polysomnography and both patients and the CG completed a self-answered questionnaire. One hundred and twenty-two patients were diagnosed as OSAS and 67 patients as non-apnoeic snorers (NAS). The self-reported number of accidents was significantly higher in OSAS patients compared with CG. The self-reported number of times off the road was significantly higher in OSAS patients compared with NAS and with CG. Variables associated with an increased risk for traffic accidents were self-reported sleepiness while driving (OR 5, 95%CI 2.3-10.9), having quit driving because of sleepiness (OR 3, 95%CI 1.1-8.6) and being currently working (OR 2.8, 95%CI 1.1-7.7). We conclude that self-reported sleepiness while driving is associated with an increased risk for traffic accidents in OSAS patients and in NAS. We suggest that this symptom can be used to alert patients and to give priority in the sleep clinic for study and treatment.

[Delayed nonspecific cutaneous hypersensitivity in extrinsic allergic alveolitis and idiopathic pulmonary fibrosis]. / Hipersensibilidad cutánea retardada inespecífica en la alveolitis alérgica extrínseca y en la fibrosis pulmonar idiopática.

BACKGROUND: A study of delayed nonspecific cutaneous hypersensitivity in extrinsic allergic alveolitis and in idiopathic pulmonary fibrosis. METHODS: 13 patients with extrinsic allergic alveolitis, 10 with idiopathic pulmonary fibrosis, 34 with sarcoidosis and a control group of 110 subjects without respiratory disease or apparent defects in cell immunity were evaluated. The skin tests of delayed hypersensitivity were carried out with five antigenic extracts (candidin, staphylococcal toxoid, tuberculin-PPD, trichophyllin, streptokinase-streptodornase). The reactions were read after 48 hours. Delayed nonspecific cutaneous hypersensitivity was globally calculated, both quantitatively (sum of the mean diameters) and quantitatively (overall average of positive reactions). RESULTS: No significant differences were found between the group of patients with idiopathic pulmonary fibrosis and the control group, nor between those with extrinsic allergic alveolitis and those with sarcoidosis. However, differences were found between the control group and the patients with extrinsic allergic alveolitis, both in the quantitative and the qualitative analysis. CONCLUSIONS: Delayed nonspecific cutaneous hypersensitivity in extrinsic allergic alveolitis is depressed in a similar way as in sarcoidosis, whereas it appears to be preserved in idiopathic pulmonary fibrosis. Therefore, extrinsic allergic alveolitis should be considered as another cause of reduction of delayed nonspecific cutaneous hypersensitivity as it is the case with sarcoidosis.

[Churg-Strauss syndrome: 8 cases in the last 10 years]. / Síndrome de Churg-Strauss. Ocho casos en los últimos diez años.

The clinical and histopathological findings of 8 patients with a diagnosis of Churg-Strauss syndrome seen in our institution in a 10 year period have been reviewed. All patients had asthma and hypereosinophilia (mean eosinophil count 7.64 x 10(9); range: 0.748 x 10(9)-31.46 x 10(9) eosinophils/l). The organs and systems involved in the late phase of the syndrome (vasculitic phase) were: nervous system (16 cases), respiratory system (5 cases), skin and subcutaneous tissue (5 cases), heart (3 cases), digestive system (3 cases) and kidney (1 case). The diagnosis was made on the basis of the clinical and histopathological findings. In 7 cases necrotizing angiitis was shown, tissue eosinophilia in 4, and extravascular granulomas in 2. In most cases, corticosteroid therapy resulted in a favorable course, but cyclophosphamide was required in two patients. In the discussion, the evolution of the criteria for the diagnosis of this condition is analyzed.

Acute delirium as a manifestation of obstructive sleep apnea syndrome.

Cognitive deficits and psychiatric manifestations such as depression and psychosis have been associated with obstructive sleep apnea (OSA) syndrome. We report a patient with OSA admitted to our center because of acute delirium of sudden onset at night, during sleep, and which impelled the patient to jump out of the window of his home. After exhaustive study, no other causes were found for the delirium, which resolved when nasal continuous positive airway pressure (nCPAP) was initiated. We believe that it is clinically important to be aware of this association, since it identifies a new, treatable cause of delirium.

Acquired factor V deficiency in a patient with pulmonary tuberculosis.

A 29 yr old man with pulmonary tuberculosis and concomitant acquired plasma coagulation factor V deficiency is reported. The case is discussed together with three previously described cases. The bleeding tendency in a patient with pulmonary tuberculosis may be caused by a coagulation factor antibody and may be corrected by chemotherapy, as in the case described. Special therapeutic approaches are required in some cases.

Impaired non-specific delayed cutaneous hypersensitivity in bird fancier's lung.

The relation between non-specific delayed cutaneous hypersensitivity and bird fancier's lung was investigated in 13 patients with the disorder. They were compared with 50 subjects who had no reason to have decreased non-specific delayed cutaneous hypersensitivity (control group) and 34 patients with pulmonary sarcoidosis. In addition, 13 patients with bird fancier's lung (11 of the original group) were tested at least one year after avoiding exposure to the causal antigen. Five antigens (candidine, staphylococcal toxoid, tuberculin purified protein derivative, trichophyton, and streptokinase-streptodornase) were injected intradermally (0.1 ml) and the mean weal diameter was measured at 48 hours. The mean weal size was significantly less in the subjects with bird fancier's lung at the time of diagnosis than in the control group (2.23 v 5.66 mm) but did not differ significantly from that of the subjects with sarcoidosis (2.80 mm) or from that of the bird fanciers with no exposure to the causal antigen for one year (2.75 mm). The impairment of non-specific delayed cutaneous hypersensitivity in patients with bird fancier's lung appears to be quantitatively similar to that occurring in sarcoidosis.