The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories.

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean±sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h(-1)) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m(-2)) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h(-1), p<0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.

Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea patients: the French multicentre study.

The percentage of compliant continuous positive airway pressure (CPAP)-treated apnoeic patients that continue to experience residual excessive sleepiness (RES) is unknown. RES was defined by an Epworth Sleepiness Scale (ESS) score of >or=11. In total, 502 patients from 37 French sleep centres using CPAP >3 h night(-1) attending their 1-yr follow-up visit were eligible. ESS and polysomnographic data as well as symptoms, quality of life, depression scores and objective CPAP compliance at 1 yr were collected. Overall, 60 patients remained sleepy on CPAP (ESS 14.3+/-2.5) leading to a prevalence rate of RES of 12.0% (95% confidence interval (CI) 9.1-14.8). After having excluded associated restless leg syndrome, major depressive disorder and narcolepsy as confounding causes, the final prevalence rate of RES was 6.0% (95% CI 3.9-8.01). Patients with RES were younger and more sleepy at diagnosis. The relative risk of having RES was 5.3 (95% CI 1.6-22.1), when ESS before treatment was >or=11. Scores of emotional and energy Nottingham Health Profile domains were two times worse in patients with RES. As 230,000 obstructive sleep apnoea patients are currently treated in France by continuous positive airway pressure, more than 13,800 of them might suffer from residual excessive sleepiness.

[Why and how to diagnose sleep respiratory disorders?]. / Pourquoi et comment diagnostiquer les troubles respiratoires du sommeil?

Gas exchange abnormalities occur firstly during sleep in restrictive and obstructive chronic respiratory failure. Nocturnal hypoxemia is often a revealing feature of a sleep-related hypoventilation/hypoxemia syndrome in patients who will have later a diurnal hypoxemia. On the other hand, sleep may induce breathing abnormalities in individuals without lung diseases, like in obstructive sleep apnea syndrome (OSAS). In OSAS, repeated closure and/or narrowing of the pharynx during sleep increases the inspiratory effort and induces sleep fragmentation. Intermittent hypoxemia is another consequence of the obstructive events in OSAS. Besides its direct consequences on sleep, OSAS is also associated with an increased risk of cardiovascular morbi-mortality. Reduced daytime alertness and cognitive functions are usually present in patients with sleep-disordered breathing. These features are believed to be related to both sleep fragmentation and nocturnal hypoxia/hypercapnia. Sleep-related hypoventilation/hypoxemia and pharyngeal obstructive events may occur together in patients with respiratory insufficiency, especially in obese and/or chronic obstructive pulmonary disease (COPD) subjects. A correct qualitative and quantitative assessment of sleep-disordered breathing may only be performed by recording specific physiological signals during sleep.

[Role of a health network dedicated to patient care for sleep disorders]. / Rôle d'un réseau de santé dans la prise en charge des troubles du sommeil.

The Réseau Morphée is a health network funded by the Regional Health Commission (Mission Régionale de Santé d'Ile-de-France). Its mission is to improve the management of sleep disorders via actions for the public, patients and health professionals. For patients suffering from sleep apnea, the network improves access to care and organises education and support groups for patients treated by Continuous Positive Airway Pressure (CPAP) in order to improve compliance. Health professionals can optimise patient care using an Internet based computerised consultation system which automatically incorporates sleep recording and CPAP reports. The expertise of the Morphée medical team is on hand at all times to help in the management of complex patients and expert advice from other members of the network is shared during regular patient management meetings. The réseau Morphée is certified as a continuing medical education (FMC) and clinical practice accreditation (EPP) organisation and so active members can validate both their FMC and EPP.

Chiari malformation and sleep related breathing disorders.

OBJECTIVE: To estimate the frequency, mechanisms and predictive factors of sleep apnoea syndrome (SAS) in a large group of children and adults with type I (CMI) and II (CMII) Chiari malformation (CM). BACKGROUND: The anatomical and functional integrity of both respiratory circuits and lower cranial nerves controlling the upper airway is necessary for breathing control during sleep. These latter structures may be altered in CM, and a few investigations have reported CM related sleep disordered breathing. METHODS: Forty-six consecutive unrelated patients with CM (40 CMI, six CMII), of which 20 were children (eight males) and 26 were adults (12 males), underwent physical, neurological and oto-rhino-laryngoscopic examination, MRI and polysomnography. RESULTS: SAS was present in 31 (67.4%) of the patients with CM (70% of CMI, 50% of CMII, including mainly children). Sixty per cent of children with CM exhibited SAS, including 35% with obstructive (OSAS) and 25% with central (CSAS) sleep apnoea syndrome. SAS was observed in 73% of CM adults (57.7% OSAS, 15.4% CSAS). Severe SAS was found in 23% of CM adults. Multiple regression analysis revealed that age, type II Chiari and vocal cord paralysis predicted the central apnoea index. CONCLUSION: SAS is highly prevalent in all age groups of patients suffering from CM. CSAS, a rare condition in the general population, was common among the patients with CM in our study. Sleep disordered breathing associated with CM may explain the high frequency of respiratory failures observed during curative surgery of CM. Our results suggest that SAS should be systematically screened for in patients with CM, especially before surgery.

Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome.

BACKGROUND AND PURPOSE: Quality of life (QOL) and sleepiness for patients with sleep apnea/hypopnea syndrome (SAHS) might improve with continuous positive airway pressure devices working in auto-adjust mode (autoCPAP) by allowing pressure modulations following patient needs. Clinical comparisons between devices driven by different algorithms are needed. METHODS: We compared the clinical effectiveness of fixed pressure CPAP and four different autoCPAP devices by assessing compliance and QOL (36-item short-form health survey [SF-36]). SAHS patients were randomly allocated to five groups. Polysomnography (PSG) was performed to titrate the effective pressure in the constant CPAP group and evaluate residual apnea/hypopnea index (AHI) under autoCPAP. Follow-up consisted of clinical visits at three and six months by homecare technicians who assessed compliance, symptom scores and SF-36 scores. A laboratory-based PSG using the same CPAP/autoCPAP device as at home was performed at six months. RESULTS: Eighty-three patients (mean age 56+/-10 yrs) with mean body mass index (BMI) 30.8+/-5.3 kg/m(2) and severe SAHS (mean AHI: 52.3+/-17.8/h) were included. There were no differences in clinical symptoms or QOL scores, and similar clinical and PSG improvements were seen in all groups. CPAP use was >5 h per night, without any significant difference between groups. CONCLUSIONS: AutoCPAP is equally as effective as fixed CPAP for long-term home treatment in severe SAHS patients.

[Evaluation of a home respiratory polygraphy system in the diagnosis of the obstructive sleep apnea syndrome]. / Evaluation d'un système de polygraphie ventilatoire dans le syndrome d'apnées du sommeil.

INTRODUCTION: Recent recommendations advise against the use of portable home respiratory polygraphy systems for the diagnosis of the obstructive sleep apnoea syndrome (OSAS). Nevertheless such systems are widely used, particularly in France. Our aim was to assess the diagnostic value of one of these systems in the diagnosis of OSAS. METHODS: 65 consecutive patients were assessed prospectively, on account of suspicion of OSAS, by home respiratory polygraphy (HRP, Medcare Embletta). HRP confirmed severe OSAS [apnoea/hypopnoea index (AHI)>30/hr] in 8 patients. Those having AHI<30 hr or a failure of HRP (5 patients) were studied by full polysomnography in the sleep laboratory (PSG). RESULTS: In 52 patients the AHI obtained by HRP and analysed manually correlated weakly with that obtained by PSG (n=52; p<0.001; r=0.36). The AHI-PSG was 27.1+/-2.8/hr and the AHI-HRP was 12+/-0.9/hr. The mean difference (HRP-PSG) was 15.1+/-37.5/hr with poor concordance. A better cut off value in terms of efficacy of HRP was an AHI of 10/hr, with sensitivity of 61.4% and a specificity of 100%. CONCLUSION: A negative result by HRP does not exclude OSAS and full PSG is required in patients suspected of having this condition.

Outcome of acetylcholinesterase deficiency for neuromuscular functioning.

Acetylcholinesterase (AChE) plays an essential role in neuromuscular transmission, therefore it is surprising that AChE knockout (KO) mice could live to the adulthood. Neuromuscular functioning in KO and normal (wild type, WT) mice were studied, at different age (1.5-, 4- and 9-month-old). Hindlimb muscle force productions in response to nerve or muscle electric stimulation were recorded in situ and in vitro. Our results show that contrary to WT mice, 1.5-, 4- and 9-month-old KO mice exhibited a decreased in tetanic force during short periods (500 ms) of repetitive nerve stimulations (tetanic fade). Nevertheless submaximal muscle forces in response to single or repetitive nerve stimulation were increased (potentiation) in 1.5-, 4- and 9-month-old KO mice as compared to WT mice (p<0.05). Tetanic fade and potentiation were absent when muscles were directly stimulated, indicating neuromuscular transmission alterations in KO mice. Contrary to younger mice, muscle weight and maximal tetanic force in response to repetitive nerve stimulation were not reduced in 4- and 9-month-old KO mice as compared to WT mice (p>0.05). In conclusion AChE deficit leads to marked neuromuscular alterations in hind limb muscle functioning and a prominent symptom is the lack of resistance to fatigue.

Vasoactive intestinal polypeptide microinjections into the oral pontine tegmentum enhance rapid eye movement sleep in the rat.

Rapid eye movement sleep can be elicited in the rat by microinjection of the cholinergic agonist carbachol into the oral pontine reticular nucleus. Intracerebroventricular administration, during the light period, of vasoactive intestinal peptide enhances rapid eye movement sleep in several species. Since this peptide is co-localized with acetylcholine in many neurons in the central nervous system, it was assumed that the oral pontine tegmentum could also be one target for vasoactive intestinal peptide to induce rapid eye movement sleep. This hypothesis was tested by recording the sleep-wakefulness cycle in freely-moving rats injected with vasoactive intestinal peptide or its fragments (1-12 and 10-28) directly into the oral pontine reticular nucleus. when administered into the posterior part of this nucleus, vasoactive intestinal peptide at 1 and 10 ng (in 0.1 microliter of saline), but not its fragments, induced a 2-fold enhancement of rapid eye movement sleep during 4 h, at the expense of wakefulness. At the dose of 10 ng, a significant increase in rapid eye movement sleep persisted for up to 8 h. Moreover, when the peptide was injected into the centre of the positive zone, rapid eye movement sleep was enhanced during three to eight consecutive days. These data provide the first evidence that rapid eye movement sleep can be elicited at both short- and long-term by a single intracerebral microinjection of vasoactive intestinal peptide. Peptidergic mechanisms, possibly in association with cholinergic mechanisms, within the caudal part of the oral pontine reticular nucleus may play a critical role in the long-term regulation of rapid eye movement sleep in rats.

Reliability of pulse oximetry during exercise in pulmonary patients.

To evaluate the reliability of pulse oximetry during exercise, we studied 101 patients primarily with chronic pulmonary diseases. Three devices were used on different patients. Radial arterial blood was sampled at rest and maximal exercise simultaneously to pulse oximetric determination. Measured blood oxygen saturation was significantly different from noninvasive saturation at rest and also at exercise for each device. Nevertheless, changes in pulse oximetry from rest to exercise were significantly correlated with measured saturation for all three devices. Direction of changes in saturation from rest to exercise was correctly evaluated by transcutaneous oximetry in all but six instances where changes were less than 4 percent. Although measured and transcutaneous saturations are significantly different, we conclude that pulse oximetry reliably estimates changes in arterial saturation between rest and exercise for a clinical purpose. None of the three tested devices was better compared with the others in estimating saturation changes at exercise.

Accuracy of respiratory inductive plethysmography during wakefulness and sleep in patients with obstructive sleep apnea.

To assess the accuracy of the respiratory inductive plethysmograph (RIP) during sleep in obese patients with obstructive sleep apnea (OSA), we monitored 13 patients with OSA during wakefulness and nocturnal sleep with simultaneous measurements of tidal volume from RIP and integrated airflow. Patients wore a tightly fitting face mask with pneumotachograph during wakefulness and sleep. Calibrations were performed during wakefulness prior to sleep and compared with subsequent wakeful calibrations at the end of the study. Patients maintained the same posture during sleep (supine, 11; lateral, two) as during calibrations. There were no significant differences in calibrations before sleep and after awakening. The mean error in 13 patients undergoing RIP measurements of tidal volume during wakefulness was -0.7 +/- 3.4 percent while that during sleep was 2.1 +/- 14.9 percent (p < 0.001). The standard deviation (SD) of the differences between individual breaths measured by RIP and integrated airflow was 9.8 +/- 5.5 percent during wakefulness and 25.5 +/- 18.6 percent during sleep (p < 0.001). During both wakefulness and sleep, errors in RIP tidal volume were not significantly correlated with body mass index. In 12 patients with at least 10 percent time in each of stages 1 and 2 sleep, SD was greater in stage 2 sleep compared with wakefulness and stage 1 (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non-REM sleep (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non REM sleep (p < 0.001). This was associated with paradoxic motion of the rib cage in two patients during REM. We conclude that, despite increased errors in individual breath measurements during sleep, more marked during stages 2 and REM sleep, RIP is clinically useful to measure ventilation quantitatively in obese patients with sleep apnea. The criterion of a decrease of 50 percent in tidal volume assessed by RIP is appropriate to define hypopneas in such patients.

Systemic hypertension in sleep apnea syndrome. Relationship with sleep architecture and breathing abnormalities.

To examine the possible relationship between systemic HT and SAS we compared 21 hypertensive (HT+) and 29 normotensive (HT-) patients for morphologic characteristics, sleep disturbances and respiratory events monitored during a full night polysomnography. There was no significant difference between HT+ and HT- patients with respect to age, weight, BMI, sleep stage distribution and disorganization, apnea-hypopnea index (number of episodes per hour of sleep) and duration (minutes per hour of sleep) nor O2 saturation indices: mean nocturnal and minimum O2 saturation. We conclude therefore that HT in SAS patients is not directly related to morphologic characteristics, sleep disturbances and breathing abnormalities.

Induction of rapid eye movement sleep by carbachol infusion into the pontine reticular formation in the rat.

Cholinergic regulation of sleep and wakefulness was studied in freely moving rats locally infused with various doses of carbachol into the pontine reticular formation. Induction of REM sleep occurred when carbachol was infused specifically into the posterior oral pontine reticular nucleus (PnO). This effect was observed with 1-10 ng of carbachol, and lasted for at least 6 h. It was antagonized by atropine (100-200 ng) infused into the same site 15 min before carbachol (10 ng), indicating that REM sleep induction resulted from the stimulation of pontine muscarinic receptors. High doses of carbachol (500 ng) did not affect REM sleep but enhanced wakefulness. Cholinergic mechanisms within the PnO may play a critical role in the regulation of REM sleep in the rat.

Carotid baroreflex control of blood pressure and heart rate in men during dynamic exercise.

The degree of control of blood pressure (BP) and heart rate (HR) by arterial baroreflex during exercise is still controversial. We studied baroreflex control of BP and HR in seven normal young men by a noninvasive procedure employing a neck suction chamber that delivers pulsatile positive and negative pressures to the carotid sinus (CS). Pressures applied to the CS ranged from -80 to +60 Torr in steps of 20 Torr. Pressure stimuli were triggered by electrocardiogram R wave, and each pressure step was maintained for 20 s in a continuous sequence. One baroreflex-response curve was obtained during the last 3 min of each 6-min period of exercise. The four levels of upright (cycle) exercise were 60, 120, 180, and 240 W, the highest requiring approximately 75% of maximal O2 uptake. The sensitivity of the HR baroreflex response assessed by linear regression of HR vs. CS pressure (CSP) did not significantly decrease from rest (-0.09 +/- 0.053 beat/Torr) to 240 W (-0.06 +/- 0.025 beat/Torr). The BP above or below which CSP was increased or decreased by neck collar pressure was significantly increased from rest (76 +/- 6.5 Torr) to 240 W (111.2 +/- 4.0 Torr). The sensitivity of baroreflex response was assessed by linear regression of BP vs. CSP and was not significantly different from rest (-0.29 +/- 0.054 Torr/Torr) up to exercise at 240 W (-0.29 +/- 0.048 Torr/Torr). We conclude that mild to severe exercise does not reduce the gain of the CS reflex below resting values.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle chemoreflex alters carotid sinus baroreflex response in humans.

The arterial baroreflex opposes pressor responses to muscle ischemia (muscle chemoreflex). Our experiments sought to quantify the unknown effects of muscle chemoreflex on carotid sinus baroreflex (CSB) sensitivity. We generated CSB stimulus-response (S-R) curves by pulsatile application (triggered by each electrocardiogram R wave) of positive and negative neck pressure (from 60 to -80 mmHg in 20-mmHg steps of 20 s each) in seven normal young men. S-R curves were obtained at rest (upright), during the last 3 min of upright cycle ergometer exercise (150 W), and at the first minute of postexercise recovery with leg circulation free (control). A second study repeated the same procedures, except that leg circulation was occluded 20 s before the end of exercise to elicit muscle chemoreflex, and occlusion was maintained during recovery measurements (approximately 3- to 4-min duration). S-R curves for CSB were shifted upward and rightward (25 mmHg) to higher arterial blood pressure (BP) by exercise and less so (10 mmHg) in recovery (free leg flow). Postexercise occlusion (muscle chemoreflex) raised BP and shifted S-R curves above exercise curves. CSB gain rose from -0.26 +/- 0.06 (control) to -0.44 +/- 0.08 (occlusion) during positive neck pressure application and was reduced from -0.14 +/- 0.04 to zero (-0.04 +/- 0.03) during negative neck pressure. Heart rate responses during postexercise muscle chemoreflex were not significantly different from control. Results reveal a nonlinear summation of CSB and muscle chemoreflex effects on BP. BP-raising capability of muscle chemoreflex enhances CSB responses to hypotension but overpowers baroreflex opposition to hypertension.

Influence of pulmonary blood flow on gas exchange in piglets.

We previously reported that O2 diffusion was limited in piglets. To test the hypothesis of an inadequacy between diffusion and perfusion in piglets (< 4 wk) vs. older pigs (> 8 wk), we compared in these two age groups the effect of an increase (by opening an arteriovenous fistula) or a decrease (by inflating a balloon in the inferior vena cava) in cardiac output (Q) on gas exchange and on the O2 equilibration coefficient D/Q beta [ratio of the diffusion capacity of O2 (D) to the product of Q and the capacitance coefficient of blood (beta)]. In piglets but not in older pigs, a decrease in Q improved the alveolar-arterial Po2 difference (P < 0.05) and D/Q beta (P < 0.05), whereas an increase in Q had the opposite effect. Changes in the alveolar-arterial O2 difference and D/Q beta were linearly correlated with Q (r = 0.75, P < 0.01 and r = 0.88, P < 0.01, respectively). We suggest that the impaired O2 diffusion in piglets was due to inadequate diffusion-perfusion equilibrium of O2.

Mechanism of improvement in pulmonary gas exchange during growth in awake piglets.

Previous studies have shown a lower arterial PO2 (PaO2) in infants and young animals than in adults. To investigate the mechanism of this impairment of gas exchange we studied 13 piglets from 12 to 65 days of age. Two days after instrumentation we measured the distribution of ventilation-perfusion ratios (VA/Q) by use of the multiple inert gas technique on awake animals. We showed that PaO2 is lower in young animals, increasing from 72 +/- 11.5 Torr before 2 wk to 102 Torr at 2 mo. This hypoxemia is due to an enlarged alveolar-arterial O2 pressure difference that significantly decreases with age. This impairment in gas exchange is not due to shunting (0.6 +/- 1.3%). Mean dead space (36 +/- 11%) was not related to age. Mean modes of perfusion and ventilation did not differ significantly between age groups. However, the dispersion of perfusion as expressed by its logSD decreased significantly with age, whereas dispersion of ventilation remained constant. Furthermore, in the young animals only, a significant difference was evidenced between measured alveolar-arterial PO2 gradient and the value predicted by the inert gas model. We therefore conclude that the impairment of gas exchange in piglets is due to two mechanisms: VA/Q mismatch and diffusion limitation for O2.

Non-invasive measurement of haemodynamics during sleep apnoea.

Sleep apnoeas are accompanied by large variations in heart rate (HR) and blood pressure (BP). This nocturnal variability in BP may be involved in the increased cardiovascular morbidity of these patients. Due to the complex interaction between asphyxia, intrathoracic pressure, cardiac function and autonomic activation, the exact haemodynamic mechanisms are unclear. To evaluate the components of the BP surges at resumption of breathing (RB) a non-invasive beat-to-beat measurement was taken of cardiac output (CO) by the pulse contour analysis of the Finapres signal. Six male normotensive patients, free of medication (37-60 y, BMI 26.5-43.0 kg m-2) were studied during polysomnography (apnoea index: 22-69 h-1). Systolic blood pressure rose from 126.5 +/- 1.3 mmHg at beginning apnoea (P1) to 140.4 +/- 1.3 at RB (P < 0.01, ANOVA). During sleep Stages 2 and 3, stroke volume decreased during RB to 96% of P1 value (NS). Due to an opposite change in HR, CO tended to rise at RB to 106% of P1. Computed total peripheral resistance rose during RB to 105% of P1 value (P < 0.011. Therefore, it is concluded that the surge in BP at RB after apnoea is due to concomitant increases in CO and in TPR. Both rises are presumably a consequence of sympathetic nervous activation by the arterial chemoreceptors.

Long-term pulmonary functional outcome of bronchopulmonary dysplasia and premature birth.

Pulmonary function and exercise tolerance were evaluated in late childhood in two groups of prematurely born children: one group with bronchopulmonary dysplasia (BPD) [n = 15; gestational age at birth (GA): 29.6 +/- 2.8 weeks; birth weight (BW): 1,367 +/- 548 g; age at test: 7.9 +/- 0.6 years], and a second group without significant neonatal lung disease [pre-term (PT)] (n = 9; GA: 30.3 +/- 1.7 weeks; BW: 1,440 +/- 376 g; age at test: 7.8 +/- 0.22 years). The results were compared with a control group of children of similar ages and heights, born at term [term born (TB)]. We observed that total lung resistance (RL) was significantly higher in BPD (11 +/- 3 cmH2O/L/s), and in PT (9 +/- 2) than in TB [5 +/- 1; (P < 0.001 and P < 0.05, respectively)]. In BPD RL was higher than in PT (P < 0.05). Dynamic lung compliance (CLdyn) was decreased in BPD (43 +/- 11 mL/cmH2O) and in PT (56 +/- 17) compared with TB (76 +/- 20) (P < 0.001 and P < 0.05), and also in BPD compared with PT (P < 0.05). Forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were lower in BPD (1.07 +/- 0.15 L and 72 +/- 7%) than in PT (1.29 +/- 0.23 L, and 80 +/- 7%) (P < 0.05). Exercise tests were performed in six boys with BPD. The ratio between minute ventilation at maximal workload (VEmax) and the predicted value of maximal voluntary ventilation (MVV) was elevated in the six BPD boys tested, compared with five boys of Group 2 and five TB boys (87 +/- 15% vs. 62 +/- 14% and 65 +/- 13%) (P < 0.05). We conclude that: 1) prematurity and BPD is followed by long-term airway obstruction and a mild degree of exercise intolerance and; 2) premature birth without BPD may be followed by a milder degree of airway obstruction in childhood than in infants who developed BPD during the neonatal period.

Increased ventilation and CO2 chemosensitivity in acetylcholinesterase knockout mice.

To investigate the effects of a permanent excess of acetylcholine (AChE) on respiration, breathing and chemosensitivity were analyzed from birth to adulthood in mice lacking the AChE gene (AChE-/-), in heterozygotes, and in control wild-type (AChE+/+) littermates. Breathing at rest and ventilatory responses to brief exposures to hypoxia (10% O2) and hypercapnia (3-5% CO2) were measured by whole-body plethysmography. At rest AChE-/- mice show larger tidal volumes (VT, + 96% in adults), overall ventilation (VE, + 70%), and mean inspiratory flow (+270%) than wild-type mice, with no change in breathing frequency (fR). AChE-/- mice have a slightly blunted response to hypoxia, but increased VE and fR responses to hypercapnia. Heterozygous animals present no consistent alterations of breathing at rest and chemosensitivity is normal. Adult AChE-/- mice have an increased VE/VO2 and a marginally higher normalized VO2. The results suggest that the hyperventilation and altered chemosensitivity in AChE-/- mice largely reflect alterations of central respiratory control.