Geraldine Nolan

Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity

Background: High C-reactive protein (CRP) and homocysteine levels are risk factors for cardiovascular disease. Some, but not all, previous studies have reported increased levels of CRP and homocysteine in patients with obstructive sleep apnoea syndrome (OSAS). A study was undertaken to investigate the levels of these factors in carefully selected patients with OSAS and matched normal controls. Methods: CRP and homocysteine levels were measured in 110 subjects following polysomnography (PSG). Non-OSAS patients (group 1) were compared with two patient groups (mild/moderate OSAS (group 2) and severe OSAS (group 3)) group-matched for body mass index (BMI), and a fourth group of patients with severe OSAS who were more obese (group 4). All were free of other disease and similar in age, smoking habits and cholesterol levels. 50 suitable patients were commenced on continuous positive airway pressure (CPAP) treatment after PSG and 49 were reassessed 6 weeks later. Results: CRP levels were similar in groups 1, 2 and 3 (median (interquartile range (IQR)) 1.11 (0.76–2.11) mg/l vs 1.82 (1.20–3.71) mg/l vs 2.20 (1.16–3.59) mg/l; p = 0.727, Kruskal-Wallis test), but were significantly higher in group 4 than in the other groups (5.36 (2.42–9.17) mg/l, p<0.05 by individual group comparisons). In multivariate analysis of all subjects, BMI was an independent predictor for CRP levels (β = 0.221; p = 0.006) but apnoea-hypopnoea index and other measures of OSAS were not. There was no difference in homocysteine levels between all four groups (p = 0.1). CPAP did not alter CRP (2.29 (1.32–4.10) vs 2.84 (1.13–5.40) mg/l; p = 0.145) or homocysteine levels (8.49 (3.66) vs 9.90 (4.72) μmol/l; p = 0.381). Conclusion: CRP and homocysteine levels are not associated with OSAS severity in men but CRP is independently associated with obesity.

Late-onset central hypoventilation syndrome: a family genetic study

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprungs disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V′R,CO2) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V′R,CO2, despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67–83%) and V′R,CO2 was 2.1 (0.03–4.3) L·min-1·kPa-1. The normal values for the authors’ centre (St Vincents University Hospital, Dublin, Ireland) are 15–40 L·min-1·kPa-1. An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.

Effects of salmeterol on sleeping oxygen saturation in chronic obstructive pulmonary disease.

Background: Sleep is associated with important adverse effects in patients with chronic obstructive pulmonary disease (COPD), such as disturbed sleep quality and gas exchange, including hypoxemia and hypercapnia. The effects of inhaled long-acting β2-agonist therapy (LABA) on these disturbances are unclear. Objectives: The aim of the study was to assess the effect of inhaled salmeterol on nocturnal sleeping arterial oxygen saturation (SaO2) and sleep quality. Methods: In a randomized, double-blind, placebo-controlled, crossover study of moderate/severe stable COPD patients, we compared the effects of 4 weeks of treatment with salmeterol 50 µg b.d. and matching placebo on sleeping SaO2 and sleep quality. Overnight polysomnography (PSG) was performed at baseline, and after 4 and 8 weeks in addition to detailed pulmonary function testing. Of 15 patients included, 12 completed the trial (median age 69 years, forced expiratory volume in 1 s, FEV1: 39%). Results: Both mean SaO2 [salmeterol vs. placebo: 92.9% (91.2, 94.7) vs. 91.0% (88.9, 94.8); p = 0.016] and the percentage of sleep spent below 90% of SaO2 [1.8% (0.0, 10.8) vs. 25.6% (0.5, 53.5); p = 0.005] improved significantly with salmeterol. Sleep quality was similar with both salmeterol and placebo on PSG. Static lung volumes, particularly trapped gas volume, tended to improve with salmeterol. Conclusion: We conclude that inhaled LABA therapy improves sleeping SaO2 without significant change in sleep quality.

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.

Severity of obstructive sleep apnoea predicts coronary artery plaque burden: a coronary computed tomographic angiography study

Obstructive sleep apnoea (OSA) is associated with significantly increased risk of cardiovascular disease. Carotid ultrasonography and retrospective, uncontrolled, coronary imaging studies have suggested an association of OSA with subclinical atherosclerosis, but there is a lack of prospective, controlled studies directly evaluating the relationship of OSA with occult coronary artery disease. We performed coronary computed tomographic angiography and inpatient-attended sleep studies on a cohort of otherwise healthy males attending our sleep laboratory, and compared coronary artery plaque volume between subjects with low and high apnoea/hypopnoea index (AHI) scores. 29 subjects participated. The median AHI was 15.5 events·h−1, with subjects who scored above this classified as high AHI. No significant differences were observed in demographic, anthropometric and clinical variables between the high- and low-AHI groups. Coronary plaque volume was significantly greater in the high-AHI group (mean plaque volume 2.6±0.7 mm2 versus 0.8±0.2 mm2; p=0.017) and, furthermore, correlated significantly with AHI (Spearman’s r=0.433; p=0.019). Following adjustment for dyslipidaemia and fasting plasma glucose levels, AHI remained a significant predictor of plaque volume (standardised &bgr;=0.424; p=0.027). In this prospective case–control study, we found that severity of OSA may predict occult coronary atherosclerosis in otherwise healthy overweight or obese male subjects. Increasing OSA severity predicts a greater burden of occult coronary artery disease in healthy overweight or obese males http://ow.ly/nSXEU

Invariant Natural Killer T Cell Deficiency and Functional Impairment in Sleep Apnea: Links to Cancer Comorbidity.

STUDY OBJECTIVES Emerging evidence links obstructive sleep apnea (OSA) with increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells play an important role in cancer immunity. We hypothesized that patients with OSA have low number of circulating invariant natural killer T (iNKT) cells, which may also be functionally impaired. This study aims to evaluate the frequency of circulating iNKT cells in OSA. DESIGN We evaluated the frequency of circulating iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24 hours on apoptosis, cytotoxicity, and cytokine production. SETTING Teaching hospital based sleep unit and research laboratory. PATIENTS Thirty-three snorers were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30). MEASUREMENTS AND RESULTS Patients with severe OSA had considerably fewer iNKT cells (0.18%) compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026. The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r = -0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% < 90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12 months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P = 0.016) and impaired cytotoxicity (P = 0.035). CONCLUSION Patients with obstructive sleep apnea (OSA) have significantly reduced levels of circulating invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell function. These observations may partly explain the increased cancer risk reported in patients with OSA.

Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis and the role of biomarkers

BACKGROUND AND OBJECTIVE Idiopathic pulmonary fibrosis (IPF) patients report fatigue, possibly reflecting sleep disturbance, but little is known about sleep-related changes. We compared ventilation and gas exchange during sleep and exercise in a cohort of IPF patients, and evaluated associations with selected biological markers. METHODS Twenty stable IPF patients (aged 67.9 ± 12.3 [SD]) underwent overnight polysomnography following an acclimatization night. Cardiopulmonary exercise testing was performed and inflammatory markers measured including TNF-α, IL-6, CXCL8, C-C motif ligand 18 (CCL-18) and C-reactive protein (CRP) RESULTS: Nine patients had sleep-disordered breathing (SDB) with an apnea-hypopnea frequency (AHI) ≥ 5/h, but only two had Epworth sleepiness score ≥ 10, thus having an obstructive sleep apnea syndrome. Sleep quality was poor. Transcutaneous carbon dioxide tension (PtcCO2) rose by 2.56 ± 1.59 kPa overnight (P = 0.001), suggesting hypoventilation. Oxygen saturation (SaO2) was lower during sleep than exercise (P < 0.01), and exercise variables correlated with resting pulmonary function. CCL-18 and CRP levels were elevated and correlated with PtcCO2 rise during sleep (P < 0.05). CCL-18 negatively correlated with diffusion capacity of carbon monoxide (DLCO), arterial oxygen (PaO2) and mean arterial carbon dioxide (PaCO2) (P < 0.05) and CRP negatively correlated with DLCO, PaO2, sleep SaO2 and oxygen uptake (VO2) during exercise (P < 0.05). CONCLUSIONS IPF patients desaturate more during sleep than exercise; thus, nocturnal pulse oxymetry could be included in clinical assessment. CCL-18 and CRP levels correlate with physiological markers of fibrosis.

Relationship between pulmonary hyperinflation and dyspnoea severity during acute exacerbations of cystic fibrosis

Acute exacerbations of cystic fibrosis (CF) occur frequently throughout the course of the disease. Dyspnoea is the most common and distressing symptom experienced by patients during these episodes. We tested the hypothesis that pulmonary hyperinflation is an important determinant of dyspnoea severity during acute exacerbations.

Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis

Dear Editor, We thank Doctors Upala and Sanguankeo1 for their interest in our paper ‘Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis and the role of biomarkers’.2 We note their conclusion from analysis of previously published clinical studies that sleep-disordered …

Contents Vol. 79, 2010

P.J. Barnes, London E.D. Bateman, Cape Town E. Brambilla, Grenoble S. Bilaceroglu, Izmir P. Camus, Dijon M. Cazzola, Rome P.N. Chhajed, Mumbai U. Costabel, Essen K. Dorrington, Oxford A. Foresi, Sesto San Giovanni M.E. Froudarakis, Alexandroupolis G. Hoheisel, Leipzig M. Humbert, Clamart M. Kneussl, Vienna J.G. Mastronarde, Columbus, Ohio L.E. Nery, São Paulo A. Palla, Pisa H.-B. Ris, Lausanne J.L. Robotham, Seattle, Wash. F. Rodriguez Panadero, Tomares International Journal of Thoracic Medicine