Upper airway obstruction during sleep in adults. Laboratory and home assessment

Ce travail présente une contribution personnelle à l’étude des phénomènes obstructifs au niveau de la voie aérienne supérieure et l’intègre dans une perspective plus large. Sont successivement abordés et discutés : - les relations entre respiration et sommeil, et particulièrement les éléments anatomiques et fonctionnels qui interviennent dans le maintien d’une perméabilité pharyngée au cours des différents états de vigilance ; les conséquences cliniques de l’obstruction de la voie aérienne supérieure pendant le sommeil, les mécanismes de cette obstruction et les différentes modalités thérapeutiques ; le traitement par pression positive continue par voie nasale, dont nous avons une large expérience, est particulièrement détaillé ; - la méthode d’étude de la respiration au cours du sommeil en laboratoire ; c’est-à-dire la polysomnographie ; nous discutons particulièrement, la synthèse et la présentation des résultats que nous avons choisies afin de mettre en évidence les relations entre les multiples données cardiorespiratoires et les stades de sommeil ; - les différents moyens d’études ambulatoires ; leurs aspects techniques et leur intérêt dans le dépistage et le suivi des patients présentant de tels problèmes respiratoires durant le sommeil sont passés en revue.Over the past decade, Upper Airway Obstruction during Sleep has been the focus of major medical interest. How this condition has so long eluded medical attention seems astonishing in view of its prevalence, of the multiple cardio-vascular and neuropsychological sequelae and the associated mortality. One reason of this fact is perhaps that the two common symptoms associated with this condition – snoring and daytime sleepiness – have long been the subject of mirth and not considered worthy of medical advice. The acknowledgement of this new condition has been the starting point of the development of new tools able to assess sleeping and breathing and of the establishment of “Sleep Disorders Centers”. As often in the medical field, pathophysiological studies of upper airway occlusion during sleep have stimulated basic work on the physiology of breathing during sleep. Important new concepts have emerged. Finally various treatment modalities, sometimes with spectacular results, have been proposed. Since 1979, I have been fortunate to be involved in these exciting developments together with respiratory and nose-throat physicians, in this institution. This thesis will integrate my own contribution in a broader perspective and examine the methods available in order to refine the clinical diagnosis, contribute to a better understanding of the pathogenesis and of the natural history of upper airway obstruction during sleep, and assess therapeutic interventions. My personal contribution encompasses the following points : - standardization of the technical conditions, data analysis and result display of cardiorespiratory sleep studies (polysomnography) in clinical setting. - demonstration of the usefulness of ambulatory wrist activity monitoring in evaluating sleep disturbance and therapeutic effects in patients with sleep apnea syndrome. - publication of the first Belgian case report of a patient with sleep apnea syndrome and his spectacular treatment by tracheostomy. - description of unusual polysomnographic features of patients with a clinical syndrome of sleep apnea but without complete apnea. - demonstration of the modifications in ventilatory response to CO2 following tracheostomy in obstructive sleep apnea. - proof of the eventual cure of sleep apnea syndrome after long-term nasal continuous positive airway pressure therapy and weight loss, in some patients with a severe form of the syndrome. - assessment of the role of nasal and pharyngeal structural abnormalities in upper airway obstruction during sleep and the benefit that ca be expected from surgery at this level. - study of anatomic and functional features observed in snorers with and without apneaThèse d'agrégation de l'enseignement supérieur (faculté de médecine) -- UCL, 199

Upper airway obstruction during nasal intermittent positive-pressure hyperventilation in sleep.

Episodes of apnoea for up to 1 min were observed in association with hypocapnia caused by passive nasal intermittent positive-pressure mechanical hyperventilation in 3 of 4 patients during sleep. Apnoea seemed to be caused by complete upper airways obstruction; we suggest that this finding was caused by active glottic closure. Avoidance of excessive hypocapnia during positive-pressure ventilation might help to avoid central-nervous-system mediated apnoeic episodes

Metachromatic leukodystrophy: Ultrastructural study of the eyes and diagnosis by conjunctival biopsy and enzyme analysis in tears

The eyes of two patients were examined by electron microscopy. The first one was affected with the infantile phenotype of metachromatic leukodystrophy, the second one with the late infantile phenotype. In both cases, the lesions were important in the optic nerve and the ciliary nerves. In the younger child, the ganglion cells of the retina and the ciliary epithelial cells were also involved, whereas these structures were normal in the older patient. Four children, affected with infantile metachromatic leukodystrophy, were examined by conjunctival biopsy. Typical lesions of the sensitive nerves were obvious and allowed the diagnosis of the disease. Two cases, affected with mucosulfatidosis, were also studied; they presented, aside from the nervous lesions, the storage of MPS-like material in the epithelial cells and the fibroblasts of the conjunctiva. The tear enzymes were assayed in most of these cases and confirmed the histopathological diagnosis by the demonstration of a deficiency of arylsulfatase A or arylsulfatase A and B, respectively in classical MLD and in mucosulfatidosis. These ultrastructural studies confirm that myelin is principally affected in sulfatidoses, and that conjunctival biopsy and enzyme analysis in tears provide an easy method for the screening of these disorders.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Failure of tonsil and nose surgery in adults with long-standing severe sleep apnea syndrome

Seven adult patients with a severe form of sleep apnea syndrome (mean apnea index, 47) underwent surgery for significant structural abnormalities at nose and/or throat level (septal deviation, turbinal hypertrophy, enlarged tonsils, long uvula, pharyngeal tumor). Although a subjective benefit was claimed by most patients, the polygraphic data showed no improvement or only a modest improvement in breathing pattern, oxyhemoglobin saturation, or general sleep architecture except in one patient. In this patient the evolution of the syndrome was recent (3 years) and surgical management of a parapharyngeal tumor resulted in a cure. We conclude that in adults with sleep apnea syndrome of long-standing, surgical correction of nasal or pharyngeal abnormalities should not be expected to normalize sleep and breathing. This contrasts with the known benefits achieved by the same type of surgery in children. Surgery might nevertheless be necessary in some adults to permit the application of other therapeutic means (ie, nasal continuous positive airway pressure)

Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation.

Azithromycin accumulates in lysosomes where it causes phospholipidosis. In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin (66 microM), the activities of sulfatase A, phospholipase A1, N-acetyl-beta-hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non-lysosomal enzymes. The level of cathepsin B mRNA was unaffected. The hyperactivity induced by azithromycin is non-reversible upon drug withdrawal, prevented by coincubation with cycloheximide, affects the Vmax but not the Km, and is not reproduced with gentamicin, another drug also causing lysosomal phospholipidosis. The data therefore suggest that azithromycin increases the level of lysosomal enzymes by a mechanism distinct from the stimulation of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis