Bertien Buyse

Respiratory dysfunction in multiple sclerosis: a prospective analysis of 60 patients

This study aimed to determine the relationship between pulmonary function, respiratory muscle function and neurological function in multiple sclerosis (MS). Sixty patients (27 males and 33 females) aged 27-75 yrs (mean +/- SD 48 +/- 12 yrs) were prospectively studied. The Kurtzke Expanded Disability Status Scale (EDSS; range 0-10) score was 6.5 +/- 1.5; and the different Functional Systems Scores (FSS; ranges 0-5 and 0-6) were: pyramidal 3.4 +/- 1.1; brain stem 1.9 +/- 1.2; mental 1.3 +/- 0.9; cerebellar 2.2 +/- 1.0; sphincter 1.8 +/- 1.5; visual 1.4 +/- 1.4; and sensory 2.0 +/- 1.5. Results of lung function tests were: vital capacity (VC) 80 +/- 23% of predicted; single-breath transfer factor of the lung for carbon monoxide (TL, CO, sb) 83 +/- 17% pred; maximal static expiratory mouth pressure (MEP) 30 +/- 16% pred; and maximal static inspiratory mouth pressure (MIP) 47 +/- 23% pred, indicating a marked respiratory muscle dysfunction, with a minor restrictive defect. In 70% of the patients, a transcutaneous oxygen saturation (Stc, O2) of less than 92% at night was found. Comparison of lung function and disability scores showed that the abnormalities in both tended to be correlated to each other, and that this was significant for EDSS versus lung volumes, for most FSS with VC, and also for some FSS with MEP and/or MIP. Duration of disease was significantly correlated with the EDSS, but not with the different FSS scores (with the exception of mental status) and not with lung function. Multiple sclerosis leads to lung function abnormalities attributable to respiratory pump dysfunction.

Treatment of chronic respiratory failure in kyphoscoliosis: oxygen or ventilation?

Patients with kyphoscoliosis and chronic respiratory insufficiency are treated either with home oxygen therapy or ventilation. Kyphoscoliotic patients demonstrate impaired ventilatory mechanics, consequently ventilation seems to be the treatment of choice. Yet, no randomised controlled trials (CRT) exist to prove it. Most investigators find it difficult to ethically justify a CRT. Therefore, the current authors performed the following retrospective study: survival and pulmonary function were analysed in all consecutive kyphoscoliotic patients who started long-term oxygen therapy (LTO group; n=15, aged 62±11 yrs (mean±sd)) or LTO plus nocturnal nasal intermittent positive pressure ventilation (nNIPPV group; n=18, aged 61±7 yrs) in the Dept of Pulmonology (University Hospital Gasthuisberg, Leuven) between 1990–2002. Prior to treatment partial pressure of oxygen (PO2) was lower, partial pressure of carbon dioxide (PCO2) tended to be higher and vital capacity (VC) tended to be lower in the nNIPPV group than in the LTO group (PO2 5.9±1 versus 6.7±0.9 kPa (44±8 versus 50±7 mmHg), PCO2 8±1 versus 7.3±0.9 kPa (60±8 versus 55±7 mmHg), VC 32±12 versus 40±16% predicted, or 645±244 versus 970±387 mL). In the nNIPPV group the 1‐yr survival was higher (100% versus 66%). nNIPPV patients demonstrated an improvement in PO2 (breathing air) +54%, PCO2 (breathing air) −21%, VC +47% and maximal static inspiratory mouth pressure +33%; these improvements were absent in the LTO group. In conclusion, nocturnal nasal intermittent positive pressure ventilation, plus long-term oxygen therapy results in more favourable survival and changes in blood gases and respiratory function than long-term oxygen therapy alone.

A Novel Algorithm for the Automatic Detection of Sleep Apnea From Single-Lead ECG

Goal: This paper presents a methodology for the automatic detection of sleep apnea from single-lead ECG. Methods: It uses two novel features derived from the ECG, and two well-known features in heart rate variability analysis, namely the standard deviation and the serial correlation coefficients of the RR interval time series. The first novel feature uses the principal components of the QRS complexes, and it describes changes in their morphology caused by an increased sympathetic activity during apnea. The second novel feature extracts the information shared between respiration and heart rate using orthogonal subspace projections. Respiratory information is derived from the ECG by means of three state-of-the-art algorithms, which are implemented and compared here. All features are used as input to a least-squares support vector machines classifier, using an RBF kernel. In total, 80 ECG recordings were included in the study. Results: Accuracies of about 85% are achieved on a minute-by-minute basis, for two independent datasets including both hypopneas and apneas together. Separation between apnea and normal recordings is achieved with 100% accuracy. In addition to apnea classification, the proposed methodology determines the contamination level of each ECG minute. Conclusion: The performances achieved are comparable with those reported in the literature for fully automated algorithms. Significance: These results indicate that the use of only ECG sensors can achieve good accuracies in the detection of sleep apnea. Moreover, the contamination level of each ECG segment can be used to automatically detect artefacts, and to highlight segments that require further visual inspection.

Relief of sleep apnoea after treatment of acromegaly: report of three cases and review of the literature

Sleep apnoea syndrome (SAS) is common in acromegalic patients. Occasionally, the relief of apnoeas after treatment of the acromegaly has been documented. We report the cases of three patients with acromegaly and severe obstructive sleep apnoea, who demonstrated a manifest improvement (respiratory disturbance index (RDI) <20) after treatment with octreotide, indicating that this drug may be effective in this disturbance. In one case, SAS disappeared although the growth hormone level was not fully normalized. This raises the intriguing hypothesis that octreotide has an effect on respiratory control or on the upper airway, that is not directly related to its action on production of growth hormone.

Cyclophosphamide rescue therapy for chronic rejection after lung transplantation

BACKGROUND Obliterative bronchiolitis remains the leading cause of late mortality after heart-lung and lung transplantation. Although several treatment options have been advocated, none has proven to be very successful. Cyclophosphamide is effective in the treatment of idiopathic pulmonary fibrosis, and chronic rejection after lung transplantation is also a fibroproliferative process. We therefore conducted an open, uncontrolled study to look at the effect of cyclophosphamide rescue therapy in the treatment of chronic rejection in lung transplant recipients. METHODS Between October 1996 and March 1998 cyclophosphamide was prescribed to 7 patients with chronic and persistent rejection who failed to respond to conventional therapy (pulse steroids or antilymphocyte products or both). RESULTS Cyclophosphamide therapy was initiated on postoperative day 478+/-366. At that time 2 patients were in bronchiolitis obliterans syndrome stage 0, 3 patients in stage 1, and 2 patients in stage 2. Their best postoperative forced expiratory volume in one second (FEV1) was 2.19+/-0.75 L. Three months before the start of cyclophosphamide the FEV1 had declined to 1.90+/-0.83 L, with a further decline to 1.63+/-0.64 L at the time of initiating cyclophosphamide. In 6 of the 7 patients the FEV1 stabilized or increased after cyclophosphamide had been started (mean FEV1 3 and 6 months after cyclophosphamide of 1.77+/-0.58 L and 1.79+/-0.48 L, respectively). One patient died 18 months after the introduction of cyclophosphamide due to progressive obliterative bronchiolitis. In one patient cyclophosphamide had to be stopped because of persistent leucopenia. CONCLUSIONS Cyclophosphamide might be a promising therapeutic alternative for the treatment of chronic persistent rejection after lung transplantation.

Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep

The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a “marker” of disease severity or a “mediator” of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation. Description of the actual approach to differential diagnosis and treatment options in central breathing disturbances http://ow.ly/QsE9304Jt8f

Noninvasive ventilation improves sleep in amyotrophic lateral sclerosis: a prospective polysomnographic study.

STUDY OBJECTIVE To evaluate the effects of noninvasive ventilation (NIV) on sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous titration with polysomnography (PSG). METHODS In this prospective observational study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were used to assess subjective sleep quality and quality of life (QoL). Patients were readmitted after one month. RESULTS In the total group, slow wave sleep and REM sleep increased and the arousal-awakening index improved. The group without bulbar involvement (non-bulbar) showed the same improvements, together with an increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved in the total and non-bulbar group. Except for oxygen saturation during REM sleep, no improvement in respiratory function or sleep structure was found in bulbar patients. However, these patients showed less room for improvement. Patient-reported outcomes showed improvement in sleep quality and QoL for the total and non-bulbar group, while bulbar patients only reported improvements in very few subscores. CONCLUSIONS This study shows an improvement of sleep architecture, carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and after one month of NIV in ALS patients. More studies are needed to identify the appropriate time to start NIV in bulbar patients. Our results suggest that accurate titration of NIV by PSG improves sleep quality. COMMENTARY A commentary on this article appears in this issue on page 511.

REM sleep-related brady-arrhythmia syndrome

Rapid eye movement (REM) sleep-related brady-arrhytmia syndrome is a cardiac rhythm disorder characterised by asystoles lasting several seconds during REM sleep in otherwise healthy individuals. In contrast to arrhythmias associated with obstructive sleep apnea, REM sleep-related sinus arrests and atrioventricular (AV) blocks are not associated with episodes of apnea or hypopnea. In literature, only few cases have been published, suggesting that the prevalence of this nighttime rhythm disorder is very rare. In this paper, we report two new cases of REM sleep-related sinus arrests and one case of REM sleep-related total AV block. To explore the underlying mechanism, an analysis of heart rate variability was performed. In a matched control population, we observed a significant lower low-to-high frequency (LF/HF) ratio in slow wave sleep as compared to REM sleep (2.04 ± 1.2 vs 4.55 ± 1.82, respectively [Mann–Whitney U test p < 0.01]), demonstrating a global increase in sympathetic activity during REM. When using the same technique in two of three patients with REM-related arrhythmias, the shift to an increased LF/HF ratio from slow wave sleep to REM sleep tended to be lower. This may reflect an increased vagal activity (HF component) during REM sleep in these subjects. We, therefore, hypothesise that, in our patients with REM sleep-related arrhythmias, the overall dominance of sympathetic activity during REM is present but to a lesser extent and temporarily switches into vagal dominance when the bursts of REMs occur. As it was still unclear whether these REM sleep-related asystoles needed to be paced, we compared our treatment and these of previously reported cases with the current American College of Cardiology/American Heart Association guidelines for implantation of cardiac pacemakers.

Robust artefact detection in long-term ECG recordings based on autocorrelation function similarity and percentile analysis

Artefacts can pose a big problem in the analysis of electrocardiogram (ECG) signals. Even though methods exist to reduce the influence of these contaminants, they are not always robust. In this work a new algorithm based on easy-to-implement tools such as autocorrelation functions, graph theory and percentile analysis is proposed. This new methodology successfully detects corrupted segments in the signal, and it can be applied to real-life problems such as for example to sleep apnea classification.

Non-invasive ventilation in amyotrophic lateral sclerosis

Abstract Non-invasive ventilation (NIV) is widely used to improve alveolar hypoventilation in amyotrophic lateral sclerosis. Several studies indicate a better survival when NIV is used, certainly in patients with none to moderate bulbar dysfunction. Data on quality of life (QoL) are rather disputable. Overall QoL is shown to be equivalent in patients with or without NIV, although health-related QoL is shown to be increased in patients with none to moderate bulbar dysfunction. NIV improves sleep quality, although patient-ventilator asynchronies are demonstrated. FVC < 50%, seated or supine, has been widely applied as threshold to initiate NIV. Today, measurements of respiratory muscle strength, nocturnal gas exchange and symptomatic complaints are used as indicators to start NIV. Being compliant with NIV therapy increases QoL and survival. Cough augmentation has an important role in appropriate NIV. Patients have today more technical options and patients with benefit from these advances are growing in number. Tracheal ventilation needs to be discussed when NIV seems impossible or becomes insufficient.