Prevalence of depression in patients referred with snoring and obstructive sleep apnoea.

BACKGROUND AND AIMS: Depression and obstructive sleep apnoea are two common entities, with common symptoms that make identification of either condition difficult. Our aim was to examine, within a group of patients referred with snoring and obstructive sleep apnoea, (i) the prevalence of depression with the 14-question Hospital Anxiety and Depression Scale (HADS), (ii) the correlation between the two lead depression symptoms from the Mini-International Neuropsychiatric Interview (MINI) and HADS, and (iii) the relationship between depression symptoms with physiological markers of OSA. METHODS: An observational study of depression questionnaires in patients referred because of snoring to a sleep clinic within university-affiliated public teaching hospital. RESULTS: Ninety-seven per cent of 240 patients approached responded, and 32% had a positive HADS (score >16/42). The HADS and MINI significantly correlated (r = 0.736, P < 0.001). Fifty-three per cent had either doctor-diagnosed depression (28%) and/or a positive HADS or MINI (25%). HADS correlated with the degree of sleepiness (r = 0.252, P < 0.0001) and inversely with hypoxaemia (r=-0.231, P < 0.0003) but not with the frequency of apnoeas and hypopnoeas (r = 0.116, P > 0.05). CONCLUSION: Depending on classification, 32-53% of patients with snoring had depressive symptoms or were on treatment, which is significantly greater than the Australian average of 21%. A simplified depression questionnaire was validated. Severity of depression correlated with sleepiness and hypoxaemia but not with severity of sleep apnoea.

Tachycardia in adults with cystic fibrosis is associated with normal autonomic function.

BACKGROUND: Whether autonomic dysfunction contributes to tachycardia in cystic fibrosis (CF) is unknown. METHODS: Heart rate variability (HRV) was assessed to determine high frequency power and the low/high frequency power ratio (HF, LF/HF) as markers of vagal and sympathovagal balance, respectively, under spontaneous and controlled breathing (15 breaths per minute (bpm)) conditions in 17 CF and 17 healthy control subjects. RESULTS: Under spontaneously breathing conditions, the CF group was tachycardic (75.4 ± 11.2 vs 60.2 ± 9.0 br/min P < 0.001) and tachypnoeic (22.6 ± 5.8 vs 13.6 ± 4.1 br/min, P= 0.001) compared with controls. No significant difference in HRV was observed between groups during spontaneous or controlled breathing. Coexistent diabetes mellitus and ß(2) agonist use were not associated with altered autonomic control. During controlled breathing, the CF group showed a negative correlation between forced expiratory volume in 1 s (FEV(1)) % predicted and HF power (P= 0.013, r=-0.59) and a positive correlation between FEV(1) % predicted and LF/HF ratio (P= 0.002, r= 0.69) suggesting an exaggerated normal vagal response. CONCLUSION: CF patients have normal autonomic function.

Cardiovascular mortality and morbidity in chronic obstructive pulmonary disease: the impact of bronchodilator treatment.

Chronic obstructive pulmonary disease (COPD) is a substantial health burden. Cardiovascular disease (CVD), the leading cause of death, frequently coexists with COPD, an effect attributed to high individual disease prevalences and shared risk factors. It has long been recognized that COPD, whether stable or during acute exacerbations, is associated with an excess of cardiac arrhythmias. Bronchodilator medications have been implicated in the excess CVD seen in COPD, either as an intrinsic medication effect or related to side-effects. Despite the theory behind increased pro-arrhythmic effects in COPD, the reported results of trials investigating this for inhaled formulations at therapeutic doses are few. Methodological flaws, retrospective analysis and inadequate adjustment for concomitant medications, including short-acting 'relief' bronchodilators and non-respiratory medications with known arrhythmia propensity, mar many of these studies. For most bronchodilators at therapeutic levels in stable COPD, we can be reassured of their safety from current studies. The exception to this is ipratropium bromide, where the current data indicate an association with increased cardiovascular adverse effects. Moreover, there is no proven benefit from combining short-acting beta-agonists with short-acting anticholinergics at high doses in the acute setting, and although this practice is widespread, it is associated with increased cardiovascular risk.

The six-minute walk test: a useful metric for the cardiopulmonary patient.

Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. The 6-min walk test (6MWT) provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. A distance less than 350 m is associated with increased mortality in chronic obstructive pulmonary disease, chronic heart failure and pulmonary arterial hypertension. Desaturation during a 6MWT is an important prognostic indicator for patients with interstitial lung disease. The 6MWT is sensitive to commonly used therapies in chronic obstructive pulmonary disease such as pulmonary rehabilitation, oxygen, long-term use of inhaled corticosteroids and lung volume reduction surgery. However, it appears less reliable to detect changes in clinical status associated with medical therapies for heart failure. A change in walking distance of more than 50 m is clinically significant in most disease states. When interpreting the results of a 6MWT, consideration should be given to choice of predictive values and the methods by which the test was carried out.

Obesity and the lung: 2. Obesity and sleep-disordered breathing.

As the prevalence of obesity increases in both the developed and the developing world, the respiratory consequences are often underappreciated. This review discusses the presentation, pathogenesis, diagnosis and management of the obstructive sleep apnoea, overlap and obesity hypoventilation syndromes. Patients with these conditions will commonly present to respiratory physicians, and recognition and effective treatment have important benefits in terms of patient quality of life and reduction in healthcare utilisation. Measures to curb the obesity epidemic are urgently required.

Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis.

BACKGROUND: The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg). METHODS: In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity. RESULTS: Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2. CONCLUSION: 6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.

Prevalence of sleepiness in surviving drivers of motor vehicle collisions.

BACKGROUND: Although alcohol and recreational drugs are recognized as significant risk factors for motor vehicle collisions (MVC), the contribution of sleepiness alone is less clear. We therefore sought to identify the contribution of sleepiness to the risk of a MVC in injured drivers, independent of drugs and alcohol. METHODS: A prospective questionnaire and examination of sleep-related risk factors in drivers surviving MVC in a major hospital-based trauma centre was carried out. RESULTS: Forty of 112 injured drivers screened were interviewed, of whom approximately 50% had at least one sleep-related risk factor, 20% having two or more. Of the MVC deemed sleep-related by questionnaire, only 25% were identified by the Australian Transport Safety Bureau definitions. Shift work was the greatest sleep-related factor identified contributing to MVC. CONCLUSION: Sleepiness, particularly related to shift work, needs to be emphasized as a risk factor for MVC. Australian Transport Safety Bureau definitions of sleep-related MVC are too lenient.

Non-invasive positive pressure ventilation for acute respiratory failure: justified or just hot air?

Non-invasive positive pressure ventilation (NIV) is the provision of mechanical positive airway pressure ventilatory support through the patient's upper airway through mask interface. Conditions in which it has been shown to be effective are acute cardiogenic pulmonary oedema and acute hypercapnic exacerbations of chronic obstructive pulmonary disease. In such conditions, NIV is associated with reduced intensive care unit demands, a reduction in intubation rates, reduced health-care expenditure and improved survival. Other conditions, such as hypercapnia of other cause, hypoxaemic respiratory failure and acute asthma, have supportive, but less conclusive data. Indications, contraindications and guidelines for the use of NIV are discussed.

Does intentional weight loss improve daytime sleepiness? A systematic review and meta-analysis.

Obesity is associated with excessive daytime sleepiness, but its causality remains unclear. We aimed to assess the extent to which intentional weight loss affects daytime sleepiness. Electronic databases were searched through 24 October 2016. Studies involving overweight or obese adults, a weight loss intervention and repeated valid measures of daytime sleepiness were included in the review. Two independent reviewers extracted data on study characteristics, main outcome (change in daytime sleepiness score standardized by standard deviation of baseline sleepiness scores), potential mediators (e.g. amount of weight loss and change in apnoea-hypopnoea index) and other co-factors (e.g. baseline demographics). Forty-two studies were included in the review. Fifteen before-and-after studies on surgical weight loss interventions showed large improvements in daytime sleepiness, with a standardized effect size of -0.97 (95% confidence interval [CI] -1.21 to -0.72). Twenty-seven studies on non-surgical weight loss interventions showed small-to-moderate improvement in daytime sleepiness, with a standardized effect size of -0.40 (95%CI -0.52 to -0.27), with no difference between controlled and before-and-after studies. We found a nonlinear association between amount of weight loss and change in daytime sleepiness. This review suggests that weight loss interventions improve daytime sleepiness, with a clear dose-response relationship. This supports the previously hypothesized causal effect of obesity on daytime sleepiness. It is important to assess and manage daytime sleepiness in obese patients.

Acute effects of continuous positive airway pressure on cardiac sympathetic tone in congestive heart failure.

BACKGROUND: Depressed ventricular performance and neurohormonal activation are key pathophysiological features of congestive heart failure (CHF). Although angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers exert beneficial effects in CHF, mortality remains unacceptably high, and the development of further therapeutic approaches is warranted. Recent data suggest that continuous positive airway pressure (CPAP) may be of benefit in the treatment of CHF, although the mechanism for this action is incompletely understood. METHODS AND RESULTS: In the present study, we examined the effect of short-term CPAP (10 cm H(2)O for 10 minutes) on hemodynamics (Swan Ganz catheter) and total systemic and cardiac sympathetic activity (norepinephrine spillover method) in 14 CHF patients in New York Heart Association class III. The application of CPAP was associated with a fall in cardiac output (4.8+/-0.3 to 4.4+/-0.2 L/min; P<0.05) and a significant reduction in cardiac norepinephrine spillover (370+/-58 to 299+/-55 pmol/min; P<0.05), although total systemic norepinephrine spillover was unchanged. CONCLUSION: The short-term application of CPAP results in an inhibition of cardiac sympathetic nervous activity. Further investigation into the potential value of long-term CPAP in CHF patients is warranted.

Effect of continuous positive airway pressure on mitral regurgitant fraction and atrial natriuretic peptide in patients with heart failure.

OBJECTIVES: We sought to determine the effects of continuous positive airway pressure (CPAP) on mitral regurgitant fraction (MRF) and plasma atrial natriuretic peptide (ANP) concentration in patients with congestive heart failure (CHF). BACKGROUND: In patients with CHF, elevated plasma ANP concentration is associated with elevated cardiac filling pressures. Secondary mitral regurgitation may contribute to elevation in plasma ANP concentration in patients with CHF. Because CPAP reduces transmural cardiac pressures and left ventricular (LV) volume, we hypothesized that long-term CPAP application would decrease the MRF and plasma ANP concentration in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). METHODS: Seventeen patients with CHF and CSR-CSA underwent baseline assessments of plasma ANP concentration and left ventricular ejection fraction (LVEF) and MRF by radionuclide angiography. They were then randomized to receive nocturnal CPAP plus optimal medical therapy (n = 9) or optimal medical therapy alone (n = 8) for 3 months and were then reassessed. RESULTS: In the CPAP-treated group, LVEF increased from (mean +/-SEM) 20.2 +/- 4.2% to 28.2 +/- 5.3% (p < 0.02); MRF decreased from 32.8 +/- 7.7% to 19.4 +/- 5.5% (p < 0.02); and plasma ANP concentration decreased from 140.9 +/- 20.8 to 103.9 +/- 17.0 pg/ml (p < 0.05). The control group experienced no significant changes in LVEF, MRF or plasma ANP concentration. Among all patients, the change in plasma ANP concentration from baseline to 3 months correlated significantly with the change in MRF (r = 0.789, p < 0.0002). CONCLUSIONS: In patients with CHF, CPAP-induced reductions in MRF and plasma ANP concentration in association with improvements in LVEF indicate improved cardiac mechanics. Our findings also suggest that reductions in plasma ANP concentration were at least partly due to reductions in MRF.

Continuous positive airway pressure increases heart rate variability in congestive heart failure.

OBJECTIVES: Our objective was to determine whether continuous positive airway pressure augments the low heart rate variability of congestive heart failure, a marker of poor prognosis. BACKGROUND: Nasal continuous positive airway pressure improves ventricular function in selected patients with heart failure. METHODS: In 21 sessions in 16 men (mean [+/- SE] age 56 +/- 2 years) with New York Heart Association functional class II to IV heart failure, we assessed the effects of 45 min with (n = 14) and without (as a time control, n = 7) nasal continuous positive airway pressure (10 cm of water) on heart rate variability and end-expiratory lung volume. Coarse-graining spectral analysis was used to derive total spectral power (PT), its nonharmonic component (fractal power [PF]) and the low (0.0 to 0.15 Hz [PL]) and high (0.15 to 0.50 Hz [PH]) frequency components of harmonic power. Standard deviation of the RR interval, high frequency power and the PH/PT ratio were used to estimate parasympathetic activity in the time and frequency domains, and the PL/PH ratio was used to estimate cardiac sympathetic activity in the frequency domain. RESULTS: Use of continuous positive airway pressure increased end-expiratory lung volume by 445 +/- 82 ml (p < 0.01) and both time (p < 0.006) and frequency domain indexes of heart rate variability: Total spectral power (p < 0.01), nonharmonic power (p < 0.023) and low (p < 0.04) and high (p < 0.05) frequency components of harmonic power all increased. Time alone had no effect on these variables. By comparison, the PH/PT ratio increased during nasal continuous positive airway pressure (p < 0.004), whereas the PL/PH ratio was unchanged. Breathing rate remained constant in both groups. CONCLUSIONS: Short-term application of nasal continuous positive airway pressure increases heart rate variability and time and frequency domain indexes of parasympathetic activity without influencing cardiac sympathetic activity. This increase may occur reflexively, through stimulation of pulmonary mechanoreceptor afferents.

Heart failure and obstructive apnoea.

Obstructive sleep apnoea (OSA) may aggravate heart failure through the mechanisms of sleep related arousals, systemic hypertension (awake and asleep) and negative intrathoracic pressure which increase cardiac afterload at times of asphyxia and hypoxaemia. Reversal of OSA with nasal continuous positive airway pressure (CPAP), in the setting of heart failure, may return cardiac function to near normal values.

Heart failure and central apnoea.

Central sleep apnoea with a Cheyne-Stokes pattern of respiration is a disorder commonly observed in patients with established symptomatic congestive heart failure (CHF). It is associated with hyperventilation and hypocapnia which are likely to result from either increased pulmonary vagal afferent nerve stimulation due to pulmonary oedema or from upregulation of chemoreceptors induced by increased sympathoneural activity. Treatment should be aimed at improving underlying cardiac function which may include angiotensin-converting enzyme inhibitors, nasal continuous positive airway pressure (CPAP) or possibly supplemental oxygen.

Hypoxemia and hypercapnia during exercise and sleep in patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF), it has been proposed that hypoxemia and hypercapnia occur during episodes of stress, such as exercise and sleep, and that respiratory muscle weakness because of malnutrition may be responsible. METHODS: Pulmonary function, respiratory muscle strength, and nutrition were assessed and correlated with the degree of hypoxemia and hypercapnia during exercise and sleep in 14 patients with CF and 8 control subjects. RESULTS: Despite no differences in maximum static inspiratory pressure (PImax) between the two groups, the CF group developed more severe hypoxemia (minimum oxyhemoglobin saturation [SpO2], 89 +/- 5% vs 96 +/- 2%; p < 0.001) and hypercapnia (maximum transcutaneous CO2 tension [PtcCO2], 43 +/- 6 vs 33 +/- 7 mm Hg; p < 0.01) during exercise. Similarly, during sleep, the CF group developed greater hypoxemia (minimum SpO2, 82 +/- 8% vs 91 +/- 2%; p < 0.005), although CO2 levels were not significantly different (maximum PtcCO2, 48 +/- 7 vs 50 +/- 2 mm Hg). Within the CF group, exercise-related hypoxemia and hypercapnia did not correlate with FEV1, residual volume/total lung capacity ratio (RV/TLC), PImax, or body mass index (BMI). Hypoxemia and hypercapnia during sleep correlated with markers of gas trapping (RV vs minimum arterial oxygen saturation [r = -0.654; p < 0.05]), RV vs maximum PtcCO2 (r = 0.878; p < 0.001), and RV/TLC vs maximum PtcCO2 (r = 0.790; p < 0.01) but not with PImax or BMI. CONCLUSION: Patients with moderately severe CF develop hypoxemia and hypercapnia during exercise and sleep to a greater extent than healthy subjects with similar respiratory muscle strength and nutritional status. Neither respiratory muscle weakness nor malnutrition are necessary to develop hypoxemia or hypercapnia during exercise or sleep.

Effects of cardiac dysfunction on non-hypercapnic central sleep apnea.

INTRODUCTION: Non-hypercapnic central sleep apnea (CSA) commonly occurs during nonrapid eye movement (non-REM) sleep in adults with congestive heart failure (CHF) and in some subjects without signs or symptoms of CHF. Hyperventilation, reduced lung volume, and circulatory delay are known to contribute to CSA, but to differing degrees depending on presence or absence of CHF. AIM: To determine whether the pattern of ventilation during sleep could be used to determine the presence of CHF. METHODS: Full polysomnographs demonstrating CSA were examined in 10 consecutive subjects with CHF and in 10 without CHF. Ventilatory, apnea, and cycle lengths, and circulation time (from the onset of ventilatory effort to the nadir of oximeter trace) were measured from cyclic apneas during non-REM sleep. RESULTS: The non-CHF group had a greater left ventricular ejection fraction (LVEF) (59.7+/-1.9% vs 19.2+/-2.2%). Circulation time (11.8+/-0.5 s vs 24.9+/-1.7 s; p < 0.001) and cycle length (35.1+/-2.8 s vs 69.5+/-4.5 s; p < 0.001) were significantly greater in the CHF group compared with the non-CHF group, but not apnea length (21.3+/-1.8 s vs 26.8+/-2.0 s; p=0.06). Ventilatory length to apnea length ratio (VL:AL) was uniformly > 1.0 in the CHF group (mean, 1.65; range, 1.02 to 2.33), and in the non-CHF group < 1.0 (mean, 0.66; range, 0.54 to 0.89). LVEF correlated negatively with both circulation time (r=-0.86; p < 0.001) and cycle length (r=-0.79; p < 0.001). CONCLUSION: The VL:AL ratio > 1.0, as well as both circulation time > 15 s and cycle length > 45 s, can be used to recognize the presence of CHF in subjects with CSA.

Sleep apnea in congestive heart failure.

Sleep-related breathing disorders, including obstructive sleep apnea (OSA) and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA), commonly occur in patients with congestive heart failure (CHF). In this setting they can have adverse pathophysiologic effects on the cardiovascular system. OSA may lead to development or progression of left ventricular (LV) dysfunction by increasing LV afterload through the combined effects of elevations in systemic blood pressure and a generation of exaggerated negative intrathoracic pressure, and by activating the sympathetic nervous system through the influence of hypoxia and arousals from sleep. Abolition of OSA by continuous positive airway pressure (CPAP) can improve cardiac function in patients with CHF. In contrast to OSA, CSR-CSA is likely a consequence rather than a cause of CHF. Here, pulmonary congestion causes hyperventilation by stimulating pulmonary irritant receptors. This leads to reductions in PaCO2 below the apneic threshold during sleep, precipitating posthyperventilatory central apneas. CSR-CSA is associated with increased mortality in CHF, probably because of sympathetic nervous system activation caused by recurrent apnea-induced hypoxia and arousals from sleep. Treatment of CSR-CSA by supplemental O2, theophylline, and CPAP can alleviate central apneas. Of these treatments, however, only CPAP has been shown to improve cardiac function and symptoms of heart failure. We conclude that effective treatments of OSA and CSR-CSA may prove to be useful adjuncts to the standard pharmacologic therapy of patients with CHF.

Sleep apnea and congestive heart failure.

Sleep apnea encompasses 2 forms of sleep disordered breathing, namely obstructive and central sleep apnea. Both these conditions are prevalent in patients with congestive heart failure (CHF) despite quite different etiology and pathogenesis. The last 15 years have seen the development of a large database of mechanistic data implicating both these conditions in the progression of cardiac dysfunction in patients with heart failure. Epidemiological data have also revealed that obstructive sleep apnea may be an independent risk factor for the development of cardiac diseases. Central sleep apnea, conversely, is more likely to emerge as a consequence of severe cardiac dysfunction, but through an elaborate vicious cycle could potentially lead to augmentation of sympathetic activity and contribute to further cardiac decline. In recent years a number of randomized controlled trials suggests secondary endpoints such as symptoms, sympatho-excitation and left ventricular function can be improved with the effective therapies available for both central and obstructive sleep apnea in patients in which these conditions co-exist. Mortality data is emerging also, and the first of a large scale mortality trial assessing the effect of attenuating central sleep apnea with continuous positive airway pressure in patients with moderate to severe CHF, is well underway. This review summarizes the important mechanistic, epidemiological and interventional studies in relation to sleep apnea and congestive heart failure with some commentary on the future direction of this rapidly growing field.