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W T McNicholas

Publications and source records attributed to W T McNicholas.

At least 19 recordsLinked to original sources
PubMed2007

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.

Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death. The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. The present report, which arose out of a European Union Cooperation in the field of Scientific and Technical Research (COST) action on OSAS (COST B26), reviews the current evidence for an independent association and proposes research priorities to identify the underlying mechanisms involved, with a view to identifying novel therapeutic strategies. Large-scale collaborative studies of carefully defined patient populations with obstructive sleep apnoea syndrome, adequately controlled for potential confounders, are needed. Such studies carry the prospect of evaluating potential interactions between different basic mechanisms operating in obstructive sleep apnoea syndrome and cardiovascular disease, and interactions with other related disorders, such as obesity, diabetes and dyslipidaemia. Furthermore, translational studies involving cell culture and animal models linked to studies of obstructive sleep apnoea syndrome patients are necessary to integrate basic mechanisms with the clinical disorder.

Cardiovascular Diseases↗
PubMed2006

Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea.

Auto-adjustable continuous positive airway pressure (APAP) devices are an emerging treatment alternative to fixed-pressure continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea syndrome. They have been engineered to automatically adjust the pressure to the optimal level on a continuous basis. However, not all APAP technologies use the same algorithm. Three different APAP devices (Autoset Spirit, Breas PV 10i and RemStar Auto) were compared in a randomised crossover trial in patients already established on fixed-pressure CPAP therapy. The outcome measures were compliance, quality of life and side-effects. Twenty-seven middle-aged patients (25 male) previously diagnosed with severe obstructive sleep apnoea syndrome (median (interquartile range) apnoea/hypopnoea index 48 (29-76)), established on CPAP therapy for >3 yrs, were randomised to each APAP device for 4 weeks. Mean pressure and patient compliance were significantly lower on the Breas PV 10i than on the other APAP devices. The devices were similar in terms of quality of life, daytime sleepiness and upper airway side-effects, but patients evaluated them significantly differently in terms of device features, sleep quality and pressure comfort, with the Breas PV 10i being the least popular. Auto-adjustable positive airway pressure devices differ in pressure delivery and patient compliance in obstructive sleep apnoea syndrome patients.

Aged↗
PubMed2004

Long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in COPD.

Oxygen desaturation occurs during sleep in severe chronic obstructive pulmonary disease (COPD), especially during rapid eye movement (REM) sleep, due to hypoventilation and ventilation-perfusion mismatching, but the possible contribution of airflow limitation is unclear. In a randomised, placebo-controlled, double-blind study of severe, stable COPD patients, the authors compared 4 weeks treatment with a long-acting inhaled anticholinergic agent (tiotropium), taken in the morning (tiotropium-AM), or in the evening (tiotropium-PM), on sleeping arterial oxygen saturation (Sa,O2) and sleep quality. Overnight polysomnography was performed at baseline and after 4 weeks treatment. A total of 95 patients with awake resting arterial oxygen tension < or = 9.98 kPa (75 mmHg) were randomised, with a mean age of 66.4 yrs and mean forced expiratory volume in one second (FEV1) of 32% predicted. A total of 80 patients completed the study, of which 56 fulfilled the polysomnographic criterion of at least 2 h sleep in both sleep study nights and represent the group analysed. Tiotropium significantly improved spirometry compared with placebo. Both tiotropium-AM and tiotropium-PM groups had higher Sa,O2 during REM than placebo (+2.41% and +2.42%, respectively, and both pooled and tiotropium-PM groups had higher Sa,O2 during total sleep time (+2.49% and +3.06%, respectively). End-of-treatment FEV1 correlated with Sa,O2 during REM sleep, however, tiotropium did not change sleep quality. Sustained anticholinergic blockade improves sleeping arterial oxygen saturation without affecting sleep quality.

Administration, Inhalation↗
PubMed2004

Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with co-existing rhinitis.

BACKGROUND: Increased nasal airflow resistance (NAR) may contribute to the pathophysiology of obstructive sleep apnoea syndrome (OSAS) but studies investigating the effects of relieving nasal obstruction in OSAS have produced differing results. There are no reports of intranasal corticosteroid therapy in adult OSAS patients with reversible nasal obstruction. METHODS: We evaluated an intranasal corticosteroid, fluticasone propionate, in 24 consecutive snorers with associated rhinitis using a randomised, placebo controlled, crossover design. Patients underwent polysomnography, snoring noise, and NAR measurements at baseline and after each 4 week treatment period. RESULTS: Twenty three patients completed the protocol and were divided into an apnoeic group (group A; 13 patients) and a non-apnoeic snoring group (group S; 10 patients) based on an apnoea-hypopnoea frequency (AHI) of > or =10/h or <10/h. AHI was significantly lower following treatment with fluticasone than with placebo in the total population (median (quartile range) 11.9 (22.6) v 20 (26.3); p<0.05) and in group A (23.3 (21.3) v 30.3 (31.9); p<0.05). Median (95% confidence interval) within subject differences for AHI were -3.2 (-17.7 to -0.2) in the total population and -6.5 (-29.5 to 1.8) in group A. NAR was also lower on fluticasone (2.74 (1.21) v 3.27 (1.38), p<0.01), within subject difference being -0.45 (95% CI -0.87 to -0.21). The changes in AHI and NAR in group A were significantly correlated (r=0.56; p<0.05). Snoring noise and sleep quality were unchanged but daily diary records indicated subjective improvements in nasal congestion and daytime alertness with fluticasone (p<0.02). CONCLUSIONS: Intranasal fluticasone is of benefit to some patients with OSAS and rhinitis. The data suggest that this form of nasal obstruction may contribute to the pathophysiology of OSAS.

Administration, Intranasal↗
PubMed2001

Reflex respiratory response to changes in upper airway pressure in the anaesthetized rat.

1. We examined the upper airway (UA) motor response to upper airway negative pressure (UANP) in the rat. We hypothesized that this response is mediated by superior laryngeal nerve (SLN) afferents and is not confined to airway dilator muscles but also involves an increase in motor drive to tongue retractor and pharyngeal constrictor muscles, reflecting a role for these muscles in stabilizing the UA. 2. Experiments were performed in 49 chloralose-anaesthetized, tracheostomized rats. Subatmospheric pressure in the range 0 to -30 cmH(2)O was applied to the isolated UA. Motor activity was recorded in separate experiments from the main trunk of the hypoglossal nerve (XII, n = 8), the pharyngeal branch of the glossopharyngeal nerve (n = 8), the medial and lateral branches of the XII (n = 8) and the pharyngeal branch of the vagus (n = 8). Afferent activity was recorded from the whole SLN in six experiments. 3. All UA motor outflows exhibited phasic inspiratory activity and this was significantly (P < 0.05) increased by UANP. Tonic end-expiratory activity increased significantly in response to pressures more negative than -20 cmH(2)O. Bilateral section of the SLN also increased (P < 0.05) motor activity and abolished the responses to UANP. Electrical stimulation of the SLN inhibited inspiratory XII activity. SLN afferents were tonically active and inhibited by UANP. 4. We conclude that UANP causes a reflex increase in motor drive to pharyngeal dilator, tongue retractor and pharyngeal constrictor muscles via afferent fibres in the SLN. Tonic activity in SLN afferent fibres at zero transmural pressure exerts a marked inhibitory effect on UA motor outflow.

Afferent Pathways↗
PubMed2001

Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease.

Hypoxaemic patients with exacerbations of chronic obstructive pulmonary disease (COPD) are at some risk of carbon dioxide (CO2) retention during oxygen therapy. We quantified the risk of CO2 retention with oxygen therapy in COPD in 24 consecutive patients presenting to the accident and emergency department with acute exacerbations associated with hypercapnic respiratory failure (partial arterial pressure of oxygen [PaO2] < 8 kPa and partial pressure of CO2 [PaCO2] > or = 6.5 kPa). Only three patients developed clinically important CO2 retention (defined as a rise in PaCO2 > 1 kPa) with controlled oxygen therapy (24-40% by Venturi mask to maintain the oxygen saturation at 91-92%). These patients presented with more severe hypercapnia, but all three required only low-flow oxygen (24-28%). These findings suggest only a small risk of aggravating hypercapnia with controlled oxygen supplementation.

Aged↗
PubMed2001

Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women.

Self-reported snoring is common in pregnancy, particularly in females with pre-eclampsia. The prevalence of inspiratory flow limitation during sleep in preeclamptic females was objectively assessed and compared with normal pregnant and nonpregnant females. Fifteen females with pre-eclampsia were compared to 15 females from each of the three trimesters of pregnancy, as well as to 15 matched nonpregnant control females (total study population, 75 subjects). All subjects had overnight monitoring of respiration, oxygen saturation, and blood pressure (BP). No group had evidence of a clinically significant sleep apnoea syndrome, but patients with pre-eclampsia spent substantially more time (31+/-8.4% of sleep period time, mean+/-SD) with evidence of inspiratory flow limitation compared to 15.5+/-2.3% in third trimester subjects and <5% in the other three groups (p=0.001). In the majority of preeclamptics, the pattern of flow limitation was of prolonged episodes lasting several minutes without associated oxygen desaturation. As expected, systolic and diastolic BPs were significantly higher in the pre-eclamptic group (p<0.001), but all groups showed a significant fall (p< or =0.05) in BP during sleep. Inspiratory flow limitation is common during sleep in patients with pre-eclampsia, which may have implications for the pathophysiology and treatment of this disorder.

Adult↗
PubMed2001

Follow-up and outcomes of nasal CPAP therapy in patients with sleep apnea syndrome.

The large and growing numbers of patients with obstructive sleep apnea syndrome (OSAS) attending sleep disorders clinics create major logistical difficulties for the follow-up of these patients, particularly those on nasal continuous positive airway pressure therapy (CPAP). Follow-up of patients on CPAP should focus on treatment efficacy, side effects, and compliance with therapy. The adequacy and comfort of mask fit and the appropriate selection of pressure level at the time of initial titration have a major influence on treatment efficacy. Outcome measures of treatment efficacy include improvements in daytime performance and quality of life measures in addition to impact on cardiovascular morbidity, particularly hypertension. Side effects and compliance with CPAP are also influenced greatly by the adequacy of mask fit and pressure selection, which underlines the great importance of adequate technical expertise and patient education at the time of initiation of therapy. The recent development of automatically adjusting CPAP devices should greatly simplify the initiation of CPAP therapy and also the subsequent follow-up of OSAS patients on CPAP therapy. However, the much higher cost of auto-CPAP devices compared to standard CPAP does not justify the routine use of these more expensive devices at this time.

Humans↗
PubMed2000

Obstructive sleep apnea syndrome: who should be treated?

Most, if not all patients referred for assessment require some form of therapeutic intervention. In particular, general lifestyle advice, sleep hygiene, and weight reduction in overweight patients should always be promoted, even where additional specific therapy such as NCPAP is also being considered. Treatment decisions are relatively easy at the extremes of the clinical spectrum, but there is an increasing choice of therapeutic options available for those patients in the mid-range of severity. Criteria based on AHI levels are inappropriate to dictate treatment choice, particularly NCPAP.

Cardiovascular Diseases↗
PubMed2000

Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome.

Cardiovascular disorders are common in patients with obstructive sleep apnoea syndrome (OSAS) but there is debate as to whether OSAS is an independent risk factor for their development, since OSAS may be associated with other disorders and risk factors that predispose to cardiovascular disease. In an effort to quantify the risk of OSAS patients for cardiovascular disease arising from these other factors, the authors assessed the future risk for cardiovascular disease among a group of 114 consecutive patients with established OSAS prior to nasal continuous positive airway pressure therapy, using an established method of risk prediction employed in the Framingham studies. Patients were 100 males, aged (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90 diastolic, 68% of patients were hypertensive. Only 18% were current smokers, while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%, 95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95% CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%; 95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive sleep apnoea syndrome patients are at high risk of future cardiovascular disease from factors other than obstructive sleep apnoea syndrome, and may help explain the difficulties in identifying a potential independent risk from obstructive sleep apnoea syndrome.

Blood Pressure↗
PubMed2000

Paradoxical vocal cord motion causing stridor after thyroidectomy.

Two women developed stridor immediately after thyroidectomy as a result of paradoxical vocal cord motion. In both cases the cord function showed a normal pattern during vocalisation but paradoxical movement was seen at laryngoscopy during tidal breathing. The abnormality improved in both patients over time with speech therapy. Whilst the syndrome of paradoxical vocal cord motion is classically thought to have a largely psychological aetiology, subtle interference with laryngeal innervation at surgery is more likely to have been the cause in these cases.

Adult↗