Biomedical subjects
J Krieger
Publications and source records attributed to J Krieger.
[Starling resister and stability of sleep ventilation].
The upper airway can be described as a collapsible segment (the pharynx) interposed between two rigid bony (the cavum) or cartilaginous (the trachea) segments. Due to this structure, the pharynx behaves as a collapsible tube, in which airflow does not depend on the downstream pressure, but is limited to a maximum value which depends only on the upstream pressure and on the pressure surrounding the collapsible segment; this behavior, known as a Starling resistor can be modeled by the waterfall effect. Thus, the upper airways can be in three different conditions: an occluded condition, in which no flow is possible, a patent condition, in which flow depends on the difference between upstream and downstream pressures (according to Poiseuille's law), and a situation in which flow is limited. The behavior of the upper airway is largely dependent on its anatomic structure, but functional factors play a critical role. Among these sleep state is both a determinant of the collapsibility of the pharynx, and determined by the simulation of upper airway mechanoreceptors whose activity depends on the activity of respiratory muscles. Thus the interplay of three factors: ventilatory drive, upper airway collapsibility, and arousal threshold can predict most of the situations of stable and unstable ventilatory behavior during sleep. The level of the arousal threshold governs the stability of the ventilatory pattern, as it determines whether a combination of slow, respiratory effort, and blood gases can be maintained or is interrupted by an arousal.
Apology. REM sleep behavior disorder: clinical and physiopathological findings.
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Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas.
Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.
Simplified diagnostic procedure for obstructive sleep apnoea syndrome: lower subsequent compliance with CPAP.
The aim of this study was to investigate whether a simplified diagnostic procedure based on ambulatory monitoring with MESAM IV altered subsequent compliance with continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) patients. During a period of 16 months, 60 patients with symptoms evocative of OSA and positive MESAM recording were prescribed CPAP after titration with standard polysomnography. Compliance was followed during 2 yrs based on built-in time counters and was compared with the compliance in two comparison groups: an equal number of equally severely affected patients diagnosed with standard polysomnography during the 18 months (8 months before and 8 months after) preceding and following the study period and a group of 48 patients with an estimated similar apnoea/hypopnoea index but less typical clinical and/or MESAM features, diagnosed as having OSA based on polysomnography during the study period. The three groups were not different by age, body mass index, or sleepiness score. Patients diagnosed with the ambulatory procedure had higher drop-out rates (21.7% versus 10% and 6.25%; p<0.05) and lower rates of use of their CPAP (43+/-0.3 h x night(-1)) than any of the control groups (53+/-0.2 and 5.6+/-0.2 h x night(-1), p<0.05). In conclusion, there is a risk that ambulatory diagnostic procedures alter the relationship of patients to their disease and/or the medical staff so that subsequent compliance with treatment may be decreased. The greatest care concerning compliance should be taken before an ambulatory-based diagnostic procedure is implemented.
Nocturnal evolution of respiratory effort in obstructive sleep apnoea syndrome: influence on arousal threshold.
It has been recently described that the overnight increase in maximal end-apnoeic oesophageal pressure (P(oes,max)), considered as an index of the arousal threshold to occlusion, mostly contributes to apnoea lengthening during the night. However, the rise in apnoea duration could also be caused by changes in hypoxaemia, chemosensitivity and upper airway resistance. To better define the relative contributions of each of these factors, we examined the recordings of nine patients. Before apnoea, the mean pulmonary resistance at peak inspiratory flow (RPIF) was computed. During apnoea, all swings in oesophageal pressure (P(oes)) were measured to define the P(oes,max), the increase from the minimum to the maximum (deltaP(oes)), the rate of increase in P(oes) (RP(oes)) and the P(oes) at the first occluded breath (P(oes,1)). A gradual and significant increase in apnoea duration (p=0.02), P(oes,max) (p=0.02) and deltaP(oes) (p=0.006) was present across the night without any changes in oxygen saturation, RPIF, and P(oes,1). The slope of increase in P(oes,max), apnoea duration and deltaP(oes) was correlated with the apnoea/hypopnoea index. We conclude that in obstructive sleep apnoea, the nocturnal rise in apnoea duration is attributable more to an increase in the arousal threshold related to apnoea recurrence than to changes in chemosensitivity and upper airway resistance.
New frontiers in the management of obstructive sleep apnoea syndrome.
This paper is the text of a talk given at the European Respiratory Society meeting in Berlin in September 1997 in a symposium organized by the Sleep Disorders Working Group. It covers new treatments for obstructive sleep apnoea which are not established as standard treatments. Although postural treatment was proposed a long time ago, few studies have investigated its efficacy in clinical practice. However, in view of the data concerning postural sleep apnoea, it certainly deserves more consideration. Oral appliances appear to have become more popular as an alternative to continuous positive airway pressure (CPAP) when surgery is not desired or not desirable. A few controlled studies have been undertaken to establish its efficacy, which is less constant and less predictable than with CPAP. Other experimental approaches include nerve and muscle stimulation, for which preliminary results are promising. In the area of drug treatment, there is nothing new. Finally, the questions of what to do when treatment does not work and who should receive treatment are addressed.
[Short-duration nocturnal hypoxemia and persistent pulmonary hypertension].
Can daily short-duration hypoxemia (4-8 hours) induce pulmonary hypertension and right ventricular hypertrophy? A clinical model of this type of hypoxemia does exist: isolated nocturnal hypoxemia in patients with obstructive sleep apnea syndrome (OSAS) or chronic obstructive pulmonary disease (COPD). By investigating the pulmonary hemodynamics of these patients, it should be possible to determine whether nocturnal hypoxemia alone can induce pulmonary hypertension. Although nocturnal hypoxemia (in OSAS as well as in COPD) can induce acute episodes of pulmonary hypertension, it would not appear that nocturnal hypoxemia alone would be sufficient to provoke permanent diurnal pulmonary hypertension. This is the conclusion of recent studies concerning diurnal pulmonary hemodynamics in OSAS and COPD patients exhibiting minimal hypoxemia during the day but significant nocturnal desaturation. The therapeutic consequences of these data, particularly in COPD are important: current evidence is insufficient to treat with nocturnal oxygen therapy COPD patients who have minimal diurnal hypoxemia but significant nocturnal desaturation.
Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones.
The influence of costimulation on the T cell response to altered peptide ligands that act as either partial or weak agonists for human CD4+ T cell clones was examined. Using stable Chinese hamster ovary (CHO) cell transfectants expressing DR2 (DRB1*1501) and human B7-1 or B7-2 as APC, presentation of native myelin basic protein (MBP) p85-99 peptide Ag or a partial agonist of MBP p85-99 induced equivalent T cell activation as measured by [3H]TdR incorporation and cytokine secretion. In marked contrast, presentation of cross-reactive peptides of MBP p85-99 that act as weak agonists with B7-1, but not B7-2, costimulation resulted in significant T cell activation as measured by [3H]TdR incorporation and cytokine secretion. These data suggest that decreasing the strength of the signal provided to the TCR allows differences in B7-1 and B7-2 signaling to be observed. Thus, the costimulatory environment during T cell activation may be a mechanism of regulating T cell cross-reactivity in the periphery.
[Excessive daytime sleepiness].
When it is not due to an extrinsic origin, somnolence may be the main symptom of various diseases. Among these causes of excessive daytime sleepiness, obstructive sleep apnea syndrome is noteworthy for its very important prevalence, estimated at 4% in adult males. Due to repeated upper airway obstructions during sleep, this disease is efficiently treated by continuous positive airway pressure applied through a nasal masks during sleep. Another syndrome, periodic limb movements during sleep may also lead to a sleep fragmentation at the origin of daytime sleepiness. Its treatment is principally based on dopaminergic agonists. Narcolepsy-cataplexy and idiopathic hypersomnia are two causes of excessive daytime sleepiness in young people. The first is as frequent as multiple sclerosis and the second is ten times less frequent. The treatment of these two diseases is now based on a new French drug: modafinil(Modiodal). Sleep pathology still has only a small place in medical training. Excessive daytime sleepiness is therefore often misdiagnosed. In addition to their major risk of work or road accidents, numerous untreated patients continue to suffer from this very unpleasant symptom, at the origin of a major social handicap.
REM sleep behavior disorder: clinical and physiopathological findings.
Abnormalities of REM sleep i.e. absence of atonia and abnormal motor control which are described in patients with REM sleep behavior disorder, have induced clinical and physiopathological interest. Initial hypothesis of a simple dysfunction of REM sleep generators has not been confirmed. The prevalence in older subjects and in patients with parkinsonian syndromes suggest that the appearance of the parasomnia is related to alteration in the neurons of pontine area i.e. nucleus peduncolopontine, in which there is an integration of sleep-wake mechanisms and locomotor systems. Controversy surrounds the specificity of absence of atonia in the diagnosis of the parasomnia. Since this polygraphic finding may be present in subjects without any sleep complaint and in patients with initial neurological impairment, diagnosis of the sleep disorders might be allowed only when the polygraphic characteristic of persistent tonus and complex motor behavior are recorded.
Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency.
The presence of human immunodeficiency virus type 1 (HIV-1) in genital secretions may be a determinant of vertical HIV-1 transmission. Cervical and vaginal secretions from HIV-1-seropositive pregnant women were evaluated to determine prevalence and correlates of HIV-1-infected cells in the genital tract. HIV-1 DNA was detected by polymerase chain reaction in 32% of 212 cervical and 10% of 215 vaginal specimens. Presence of HIV-1 DNA in the cervix was associated with cervical mucopus and a significantly lower absolute CD4 cell count (354 vs. 469, P < .001). An absolute CD4 cell count <200 was associated with a 9.6-fold increased odds of cervical HIV-1 DNA detection compared with a count > or = 500 (95% confidence interval, 2.8-34.2). Detection of vaginal HIV- 1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin A deficiency. Presence of HIV-1-infected cells in genital secretions was associated with immunosuppression and abnormal cervical or vaginal discharge.
Sleep-related hypoxaemia in chronic obstructive pulmonary disease: causes, consequences and treatment.
Worsening of hypoxaemia during sleep in patients with chronic obstructive pulmonary disease has been extensively investigated in the past 20 years owing to the development of polysomnography and to the advent of reliable transcutaneous oximeters. Sleep-related hypoxaemia is characteristic of rapid-eye-movement (REM) sleep but may be present during other sleep stages. There is a strong relationship between nocturnal O2 saturation and the level of daytime PaO2: the more pronounced daytime hypoxaemia, the more severe nocturnal hypoxaemia. Sleep-related hypoxaemia is due to a variable combination of alveolar hypoventilation and ventilation-perfusion mismatching, alveolar hypoventilation being the preponderant mechanism during REM sleep. The deleterious effects of sleep-related hypoxaemia include cardiac arrhythmias, 'hypoxaemic stress' on the coronary circulation and especially, peaks of pulmonary hypertension. The treatment of nocturnal hypoxaemia is conventional O2 therapy (both nighttime and daytime) in patients who exhibit marked daytime hypoxaemia (PaO2 < 55-60 mm Hg). At present data are not sufficient for justifying the use of isolated nocturnal O2 therapy in patients with nocturnal desaturation who do not qualify for conventional O2 therapy.
Five-year effects of nasal continuous positive airway pressure in obstructive sleep apnoea syndrome.
There have been very few studies assessing the long-term physiological effects of nasal continuous positive airway pressure (CPAP) for the obstructive sleep apnoea syndrome. We therefore investigated prospectively the evolution of lung function, arterial blood gases and pulmonary haemodynamics in patients with this syndrome treated with CPAP. Sixty five patients were included. The mean duration of home treatment with nasal CPAP was 64+/-6 months. Most of the patients (77%) were smokers at the baseline assessment. We observed a small, but significant, decrease in forced expiratory volume in one second (FEV1) from 80+/-21% at baseline (t0) to 76+/-21% of the predicted value at the follow-up evaluation (t5) (p<0.01). Arterial oxygen tension (P[a,O2]) for the group as a whole remained stable (9.4+/-1.5 kPa (71+/-11 mmHg) versus 9.4+/-1.2 kPa (71+/-9 mmHg)). However, P(a,O2) increased in the subgroup of patients with hypoxaemia at t0 (n=23), from 7.8+/-0.7 kPa (59+/-5 mmHg) to 8.9+/-1.2 kPa (67+/-9 mmHg). Arterial carbon dioxide tension (P[a,CO2]) for the group as a whole increased slightly, but significantly, from 5.2+/-0.7 kPa (39+/-5 mmHg) to 5.4+/-0.5 kPa (41+/-4 mmHg) (p<0.05). Mean pulmonary artery pressure (Ppa) at rest did not change (16+/-5 mmHg versus 17+/-5 mmHg; NS) nor did exercising Ppa. In the 11 patients with pulmonary hypertension at t0, Ppa was 24+/-5 mmHg at t0 versus 20+/-7 mmHg at t5 (NS). We conclude that the significant decrease of forced expiratory volume in one second after 5 yr follow-up was related to a high percentage of smokers and exsmokers in the study population. Daytime arterial oxygen tension and pulmonary artery pressure remained stable in an unselected series of 65 obstructive sleep apnoea syndrome patients treated for 5 yrs with nasal continuous positive airway pressure, unlike arterial carbon dioxide tension, which increased by a small, but significant, amount.
Respiratory effort during obstructive sleep apnea: role of age and sleep state.
OBJECTIVE: To evaluate the patients' individual characteristics predictive of the degree of respiratory effort developed during obstructive sleep apneas (OSAs). DESIGN: Prospective consecutive sample, collection of clinical and polysomnographic data. SETTING: University teaching hospital. PATIENTS: One hundred sixteen consecutive OSA patients with clinical symptoms of OSA and more than 20 apneas per hour of sleep. MEASUREMENTS: Anthropomorphic data, daytime blood gas values, and polysomnographic data. From esophageal pressure measurements during sleep, three indexes of respiratory effort during OSAs were derived: the maximal end-apneic esophageal pressure swing (PesMax), the increase in esophageal pressure swing (deltaPes) during the apnea, and its ratio to apnea duration (RPes). RESULTS: The indexes of respiratory effort were significantly lower in rapid eye movement (REM) than in non-REM sleep (PesMax: 50.9+/-2.5 vs 39.6+/-1.9 cm H2O, p<0.001; deltaPes: 30.9+/-1.7 vs 23.4+/-1.4 cm H2O, p<0.001; RPes: 1.05+/-0.05 vs 0.53+/-0.03 cm H2O/s, p<0.001); therefore, a separate analysis was conducted in non-REM and in REM sleep. Indexes were also significantly lower in subgroups of older as compared to younger patients (PesMax: 55.6+/-3.5 vs 40.0+/-2.2 cm H2O, p<0.001; deltaPes: 34.2+/-2.3 vs 24.1+/-1.6 cm H2O, p=0.001; RPes: 1.21+/-0.08 vs 0.8+/-0.05 cm H2O/s, p<0.001). The three indexes were closely correlated with each other and only PesMax correlation data are reported. In non-REM sleep, age was the most important single independent correlate of PesMax (r=-0.37, p=0.000). In REM sleep, the apnea-related hypoxemia, apnea duration, and age were the main contributors to the variance of PesMax. CONCLUSIONS: Respiratory effort in response to upper airway occlusion in OSA patients is lower in REM than in non-REM sleep and decreases with increasing age.
Accidents in obstructive sleep apnea patients treated with nasal continuous positive airway pressure: a prospective study. The Working Group ANTADIR, Paris and CRESGE, Lille, France. Association Nationale de Traitement à Domicile des Insuffisants Respiratoires.
Many studies have shown a relationship between obstructive sleep apnea (OSA) and accidents, but to our knowledge, none have investigated prospectively the effects of treatment with nasal continuous positive airway pressure (CPAP). CPAP was proposed to 973 patients, of whom 893 patients actually underwent CPAP. These patients were consecutively invited to enter a prospective follow-up study including a questionnaire before treatment and after 6 and 12 months of treatment; 547 patients completed the study (153 left the study, and only partial data were available for 193). The baseline questionnaire included questions concerning accidents in the previous 12 months, asking whether patients had had an accident and, if so, whether they felt that the accident(s) were related to sleepiness, and whether the patients felt that they had had near-miss accidents due to sleepiness. The questionnaires at 6 and 12 months included the same questions referring to the previous 6 months; the accidents reported on each follow-up questionnaire were cumulated and compared with the accidents during the 1-year period before treatment. The number of patients having an accident decreased with treatment for real accidents (from 60 to 36; p<0.01), as well as for near-miss accidents (from 151 to 32; p<0.01). The average number of accidents per patient also decreased, for real accidents (from 1.6+/-1.3 to 1.1+/-0.3; p<0.01) and for near-miss accidents (from 4.5+/-6.5 to 1.8+/-1.4; p<0.01). The cost, in terms of days in hospital related to accidents, decreased from 885 to 84 days. With caution due to the absence of a control group, it is suggested that treatment with CPAP decreases the number of accidents occurring in OSA patients. This result may have important implications in the evaluation of the cost/benefit ratio when treating OSA patients.