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.

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.

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.

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.

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.

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.

Obstructive sleep apnoea and cardiovascular disease.

Obstructive sleep apnoea (OSA) leads to both acute and chronic physiological effects on the cardiovascular system. There is now a large amount of evidence showing that OSA is independently associated with a wide spectrum of clinical cardiovascular disease (CVD). Evidence for a causative effect of OSA is strongest for hypertension, but is weaker for other cardiovascular disorders. Large prospective trials are ongoing and when results become available the link between OSA and CVD is likely to be strengthened. Treatment of OSA with continuous positive airway pressure has been shown to improve blood pressure, particularly in those with hypertension, and also left ventricular ejection fraction in those with congestive heart failure. Given the high prevalence of OSA in the community and its effects on the cardiovascular system, symptoms of this disorder should be sought in patients being investigated or treated for CVD.

Increased long-term mortality in heart failure due to sleep apnoea is not yet proven.

Previous small-scale studies of the effect of sleep-disordered breathing (SDB) on prognosis in congestive heart failure (CHF) are either lacking or conflicting. The aim of this study was to assess the impact of the presence and type of SDB on mortality in a patient group with severe CHF referred to a specialised heart failure centre. Out of 78 patients ((mean +/- SD) 53 +/- 9 yrs, left ventricular ejection fraction 19.9 +/- 7.2% and pulmonary capillary wedge pressure 16.5 +/- 8.3 mmHg) followed-up over a median period of 52 months, 29% had no apnoea (CHF-N), 28% had obstructive sleep apnoea (CHF-OSA) and 42% had central sleep apnoea (CHF-CSA). At 52 months, their overall mortality was 40%, and combined mortality and transplantation was 72%. Mortality rates were similar between the three apnoea groups. Survivors had a similar prevalence of SDB (71%) as the nonsurvivors (70%). Although a significant increase in mortality was evident at 500 days in those patients with either CHF-SDB or CHF-CSA as compared with CHF-N, this was not significant at final follow-up (52 months) using Kaplan Meier analysis. Multivariate analysis identified transplantation but not SDB type or severity as a significant predictor of survival. In conclusion, sleep-disordered breathing impacts upon early (500 day), but not long-term (52 month), mortality in a specialised heart failure centre.

Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis.

BACKGROUND: Chest physiotherapy is essential to the management of cystic fibrosis (CF). However, respiratory muscle fatigue and oxygen desaturation during treatment have been reported. The aim of this study was to determine whether non-invasive ventilation (NIV) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF. METHODS: Twenty six patients of mean (SD) age 27 (6) years and forced expiratory volume in 1 second (FEV1) 34 (12)% predicted completed a randomised crossover trial comparing standard treatment (active cycle of breathing technique, ACBT) with ACBT + NIV. Respiratory muscle strength (PImax, PEmax), spirometric parameters, and dyspnoea were measured before and after treatment. Pulse oximetry (SpO2) was recorded during treatment. Sputum production during treatment and 4 and 24 hours after treatment was evaluated. RESULTS: There was a significant reduction in PImax following standard treatment that was correlated with baseline PImax (r=0.73, p<0.001). PImax was maintained following NIV (mean difference from standard treatment 9.04 cm H2O, 95% confidence interval (CI) 4.25 to 13.83 cm H2O, p=0.006). A significant increase in PEmax was observed following the NIV session (8.04 cm H2O, 95% CI 0.61 to 15.46 cm H2O, p=0.02). The proportion of treatment time with SpO2 < or =90% was correlated with FEV1 (r=-0.65, p<0.001). NIV improved mean SpO2 (p<0.001) and reduced dyspnoea (p=0.02). There were no differences in FEV1, forced vital capacity (FVC) or sputum weight, but FEF(25-75) increased following NIV (p=0.006). CONCLUSION: Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF. Addition of NIV improves inspiratory muscle function, oxygen saturation and small airway function and reduces dyspnoea.

The Victorian CPAP program: is there a need for additional education and support?

BACKGROUND: The Victorian Continuous Positive Airways Pressure (CPAP) Program provides CPAP services to financially disadvantaged individuals with moderate to severe sleep apnoea. AIMS: To evaluate health outcomes in patients referred to the pilot program in order to: (i) assess the magnitude of health benefit from treatment in this highly selected population and (ii) identify patient characteristics or factors related to service provision that may influence outcome. METHODS: We adopted a simple before-after research design. Patients who were referred to the program were recruited from five sleep centres. Questionnaires were administered at baseline and 1 and 3 months after commencing CPAP. Generic and disease-specific quality of life were assessed using the MOS 36-Item Short-form Health Survey and the Sleep Apnoea Quality-of-life Index, respectively. Subjective daytime sleepiness was measured using the Epworth Sleepiness Scale and the Sleep-Wake Activity Inventory. RESULTS: Of the 68 subjects enrolled in the study, 59 were available for follow up. There were significant improvements in daytime sleepiness (P < 0.0005). Treatment-related symptoms had a negative impact on overall disease-specific quality of life, however there were significant improvements in all other domains of disease-specific quality of life (P < 0.0005). Improvements in generic quality of life were small but statistically significant (P < 0.05). Hospital, disease severity, baseline sleepiness, gender and CPAP-machine type were not predictors of outcome (P > 0.05). CONCLUSION: This review of the Victorian CPAP Program identified significant improvements in subjective daytime sleepiness and quality of life, despite the negative impact of treatment-related symptoms. Future research should explore whether services can be modified to help reduce the impact of treatment-related side-effects.

Cardiac diastolic function and hypercapnic ventilatory responses in central sleep apnoea.

Hyperventilation is the key factor contributing to the development of idiopathic nonhypercapnic central sleep apnoea (ICSA), where left ventricular systolic function is normal. ICSA is reported to occur in 20% of patients with left ventricular diastolic dysfunction, in whom elevated pulmonary vascular pressures and resultant increased pulmonary vagal afferent traffic may contribute to hyperventilation. The contribution of the two potential mechanisms responsible for the hyperventilation seen in the following ICSA was measured: 1) left ventricular diastolic dysfunction-induced pulmonary hypertension; and 2) increased peripheral and central hypercapnic ventilatory responses (HCVR). The pulmonary artery pressure, left ventricular diastolic function and chemosensitivity to hypercapnia were measured during wakefulness in 16 subjects with ICSA. All subjects had systolic pulmonary artery pressures <3.99 kPa (<30 mmHg) and only four had diastolic dysfunction. All subjects had elevated peripheral and central HCVR compared with historical normal control subjects. Diastolic dysfunction correlated with increasing age but not with HCVR or markers of central sleep apnoea severity. Idiopathic nonhypercapnic central sleep apnoea is likely to be dependent upon raised hypercapnic ventilatory responses, and not pulmonary hypertension due to left ventricular diastolic dysfunction.