Increased alveolar nitric oxide concentration is related to nocturnal oxygen desaturation in obstructive sleep apnoea.

PURPOSE: To assess distal/alveolar inflammation in patients with suggestive symptoms of obstructive sleep apnoea (OSA) using exhaled nitric oxide (NO) measured by two-compartment model (2-CM) after correction for axial NO back-diffusion (trumpet model). METHODS: Ninety five patients suspected for OSA prospectively underwent pulmonary function test, overnight polysomnography (PSG), and exhaled NO measurement. Patients with apnoea-hypopnoea index (AHI) < 5/hour were included in non-OSA group. Exhaled NO was repeatedly measured after PSG in 21 OSA patients and 8 non-OSA subjects. RESULTS: Alveolar NO concentration (C(ANO)) was significantly higher in OSA patients (n = 71; 4.07 ± 1.7 ppb) as compared with non-OSA subjects (n = 24; 2.24 ± 1.06 ppb; p < 0.0001) whilst maximal bronchial NO flux (J'awNO) and fractional exhaled NO (F(ENO)) did not differ between the two groups. C(ANO) was strongly associated to AHI (r = 0.701; p < 0.0001) and to recording time with SaO2 < 90% (ST-90%; r = 0.659; p < 0.0001) in OSA patients but not in non-OSA persons. The area under ROC curve for screening patients with OSA and significant nocturnal oxygen desaturation (ST-90% > 1%) was 0.865 ± 0.036 (95% IC, 0.793-0.937; p < 0.0001). C(ANO) at 4.5 ppb could detect these patients with specificity of 94% and sensitivity of 46%. Increase of C(ANO) measured after PSG was significantly related to oxygen desaturation index (ST-90%) in OSA patients. CONCLUSIONS: Increased alveolar NO concentration was related to the severity of nocturnal oxygen desaturation in patients with OSA, linking the distal airway inflammation to intermittent hypoxia. (250 words).

Cardiovascular comorbidities in obstructive sleep apnoea according to age: a sleep clinic population study.

PURPOSE: To describe the features of obstructive sleep apnoea (OSA) and its association with arterial hypertension (HT), coronary artery disease (CAD), and arrhythmias in elderly (≥65 years) versus younger patients. METHODS: All adult patients referred to our Sleep Research Unit for suspected OSA were included and underwent a thorough medical examination and an in-laboratory polysomnography. The severity of OSA was defined by the apnoea-hypopnoea index (AHI) as mild [5-15/h), moderate [15-30/h), and severe (≥30/h). RESULTS: Elderly patients (n = 136) and really old patients (>75 years) had higher prevalence of OSA (89 %) and severe OSA (36.8 %) as compared to younger patients (n = 439; 79.5 and 27.6 %, respectively, p < 0.05). In patients with OSA, the elderly group had a poorer sleep quality and more severe nocturnal oxygen desaturation than the younger group. Elderly patients presented higher percentages of HT (47.8 %), CAD (19.8 %), and arrhythmias (16.2 %) as compared to younger patients (p < 0.01). The odds ratio (OR) for HT increased with OSA severity from 1.0 to 1.65 (95 % confidence interval 0.83-3.27), 1.0 to 2.5 (95 % CI 1.25-5.00), and 1.0 to 3.77 (1.95-7.29) in younger patients, but not in elderly ones where the OR increased from 1.0 to 0.6 (0.17-2.04), 1.0 to 1.14 (0.34-3.82), and 1.0 to 1.46 (0.46-4.63), respectively. CONCLUSION: Stronger relation of HT and OSA severity in younger patients should encourage us to screen OSA in these patients at very young age. Increased OSA severity without obesity in very old patients needs to be confirmed and further studied.

Value of EEG reactivity for prediction of neurologic outcome after cardiac arrest: Insights from the Parisian registry.

PURPOSE: To evaluate the predictive value of EEG reactivity assessment and confounders for neurological outcome after cardiac arrest. METHODS: All consecutive patients admitted in a tertiary cardiac arrest center between 2007 and 2016 still alive 48 h after admission with at least one EEG recorded during coma. EEG reactivity was defined as a reproducible waveform change in amplitude or frequency following standardized stimulation. Each EEG was classified based on American Clinical Neurophysiology Society nomenclatures and classified in highly malignant (including status epilepticus), malignant, or benign EEG. We assessed the predictive values of EEG reactivity and sedation effect for neurologic outcome at ICU discharge using the Cerebral Performance Category scale (with CPC 1-2 assumed as favorable outcome and CPC 3-4-5 considered as poor outcome). RESULTS: Among 428 patients, a poor outcome was observed in 80% patients. The median time to EEG recording was 3 (1-4) days and 51% patients had a non-reactive EEG. The positive predictive value (PPV) of a non-reactive EEG to predict an unfavorable outcome was 97.1% (IC95% 93.6-98.9), increasing to 98.3% (IC95 94.1-99.8) when the EEG had been performed without sedation. In multivariate analysis, a non-reactive EEG was associated with poor outcome (OR 12.6 IC95% 4.7-33.6; p < 0.001). In multivariate analysis, concomitant sedation was not statistically associated with EEG non-reactivity. The PPV of a benign EEG to predict favorable outcome was 49.7% (IC95% 41.5-57.9), increasing to 66.2% (IC95% 54.3-76.8) when EEG was recorded earlier, with ongoing sedation. CONCLUSIONS: After cardiac arrest, absence of EEG reactivity was predictive of unfavorable outcome. By contrast, a benign EEG was slightly predictive of a favorable outcome. Reactivity assessment may have important implications in the neuroprognostication process after cardiac arrest and could be influenced by sedation.

In vivo electrotransfer of the cardiotrophin-1 gene into skeletal muscle slows down progression of motor neuron degeneration in pmn mice.

Among all vectors designed for gene therapy purposes, adenovirus appears to be the most efficient in vivo vehicle to transduce the broadest spectrum of cellular targets. However, the deleterious immunogenicity of this viral vector impedes its use in chronic diseases. Non-viral vectors, such as naked DNA, are attractive alternatives for safety and technical issues, such as scale-up production. Naked DNA injection, greatly improved when combined with electroporation, showed great potential in adult animals, especially when directed to the muscle. We have recently proven the therapeutic effect of a neonatal single intramuscular injection of a cardiotrophin-1 (CT-1)-encoding adenovirus in a hereditary disease mouse model of human motor neuron disease, the progressive motor neuronopathy (pmn) mutant. We now demonstrate that a single injection/electroporation of a CT-1-encoding plasmid in neonate pmn mice is almost as efficient as adenovirus-mediated gene transfer with respect to survival, muscular function and neuroprotection of the animals. Treated mice gain global weight, their mean lifespan is extended by 25%, all their electromyographic parameters are improved and myelinated axons of their phrenic nerves are protected. Moreover, we show that re-injection/electroporation leads to improvements in this neuroprotection. We therefore demonstrate for the first time the therapeutic efficacy of neonatal intramuscular DNA injection/electroporation in a murine model of a human hereditary disorder.