Managing fatigue in sarcoidosis – a systematic review of the evidence

Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended

Introducing a core curriculum for respiratory sleep practitioners

The background and purpose of the HERMES (Harmonising Education in Respiratory Medicine for European Specialists) initiative has been discussed at length in previous articles [1-3]. This article aims to provide more detailed and specific insight into the process and methodology of the Sleep HERMES Task Force in developing a core curriculum in respiratory sleep medicine

The evaluation of a novel single-lead biopotential device for home sleep testing

Study Objectives: This paper reports on the clinical evaluation of the sleep staging performance of a novel single-lead biopotential device. Methods: One hundred and thirty-three patients suspected of obstructive sleep apnea were included in a multi-site cohort. All patients underwent polysomnography and received the study device, a single-lead biopotential measurement device attached to the forehead. Clinical endpoint parameters were selected to evaluate the device's ability to determine sleep stages. Finally, the device's performance was compared to the clinical study results of comparable devices. Results: Concurrent PSG and study device data were successfully acquired for 106 of the 133 included patients. The results of this study demonstrated significant similarity in overall sleep staging performance (five-stage Cohen's Kappa of 0.70) to the best-performing reduced-lead biopotential device to which it was compared (five-stage Cohen's Kappa of 0.73). Contrary to the comparator devices, the study device reported a higher Cohen's Kappa for rapid eye movement (REM) (0.78) compared to N3 (0.61), which can be explained by its particular measuring electrode placement (diagonally across the lateral cross-section of the eye). This placement was optimized to ensure the polarity of rapid eye movements could be adequately captured, enhancing the capacity to discriminate between N3 and REM sleep when using only a single-lead setup. Conclusions: The results of this study demonstrate the feasibility of incorporating a single-lead biopotential extension in a reduced-channel home sleep apnea testing setup. Such incorporation could narrow the gap in the functionality of reduced-channel home sleep testing and in-lab polysomnography without compromising the patient's ease of use and comfort.</p

Pitolisant for Daytime Sleepiness in Patients with Obstructive Sleep Apnea Who Refuse Continuous Positive Airway Pressure Treatment A Randomized Trial

Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mgld over 12 weeks. The primary endpoint was the change in the Epworth Sleepiness Scale score. Key secondary endpoints were maintenance of wakefulness assessed on the basis of the Oxford Sleep Resistance test, safety, Clinical Global Impression of severity, patient's global opinion, EuroQol quality-of-life questionnaire, and Pichot fatigue questionnaire. Measurements and Main Results: A total of 268 patients with obstructive sleep apnea (75% male; mean age, 52 yr; apnea-hypopnea index, 49/h; baseline sleepiness score, 15.7) were randomized (200 to pitolisant and 68 to placebo) and analyzed on an intention-to-treat basis. The Epworth Sleepiness Scale score was reduced more with pitolisant than with placebo (-2.8; 95% confidence interval, -4.0 to -1.5; P <0.001). Wake maintenance tests were not improved. The Pichot fatigue score was reduced with pitolisant. The overall impact of pitolisant was confirmed by both physicians' and patients' questionnaires. Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns. Conclusions: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.Peer reviewe

A multicentric validation study of a novel home sleep apnea test based on peripheral arterial tonometry

Study Objectives This paper reports on the multicentric validation of a novel FDA-cleared home sleep apnea test based on peripheral arterial tonometry (PAT HSAT). Methods One hundred sixty-seven participants suspected of having obstructive sleep apnea (OSA) were included in a multicentric cohort. All patients underwent simultaneous polysomnography (PSG) and PAT HSAT, and all PSG data were independently double scored using both the recommended 1A rule for hypopnea, requiring a 3% desaturation or arousal (3% Rule), and the acceptable 1B rule for hypopnea, requiring a 4% desaturation (4% Rule). The double-scoring of PSG enabled a comparison of the agreement between PAT HSAT and PSG to the inter-rater agreement of PSG. Clinical endpoint parameters were selected to evaluate the device’s ability to determine the OSA severity category. Finally, a correction for near-boundary apnea–hypopnea index values was proposed to adequately handle the inter-rater variability of the PSG benchmark. Results For both the 3% and the 4% Rules, most endpoint parameters showed a close agreement with PSG. The 4-way OSA severity categorization accuracy of PAT HSAT was strong, but nevertheless lower than the inter-rater agreement of PSG (70% vs 77% for the 3% Rule and 78% vs 81% for the 4% Rule). Conclusions This paper reported on a multitude of robust endpoint parameters, in particular OSA severity categorization accuracies, while also benchmarking clinical performances against double-scored PSG. This study demonstrated strong agreement of PAT HSAT with PSG. The results of this study also suggest that different brands of PAT HSAT may have distinct clinical performance characteristics

Investigation and management of residual sleepiness in CPAP-treated patients with obstructive sleep apnoea: the European view

Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnoea (OSA), defined as the inability to stay awake during the day. Its clinical descriptors remain elusive, and the pathogenesis is complex, with disorders such as insufficient sleep and depression commonly associated. Subjective EDS can be evaluated using the Epworth Sleepiness Scale, in which the patient reports the probability of dozing in certain situations; however, its reliability has been challenged. Objective tests such as the multiple sleep latency test or the maintenance of wakefulness test are not commonly used in patients with OSA, since they require nocturnal polysomnography, daytime testing and are expensive. Drugs for EDS are available in the United States but were discontinued in Europe some time ago. For European respiratory physicians, treatment of EDS with medication is new and they may lack experience in pharmacological treatment of EDS, while novel wake-promoting drugs have been recently developed and approved for clinical use in OSA patients in the USA and Europe. This review will discuss 1) the potential prognostic significance of EDS in OSA patients at diagnosis, 2) the prevalence and predictors of residual EDS in treated OSA patients, and 3) the evolution of therapy for EDS specifically for Europe

Sleep disorders in COPD: the forgotten dimension

Sleep in chronic obstructive pulmonary disease (COPD) is commonly associated with oxygen desaturation, which may exceed the degree of desaturation during maximum exercise, both subjectively and objectively impairing sleep quality. The mechanisms of desaturation include hypoventilation and ventilation to perfusion mismatching. The consequences of this desaturation include cardiac arrhythmias, pulmonary hypertension and nocturnal death, especially during acute exacerbations. Coexistence of COPD and obstructive sleep apnoea (OSA), referred to as overlap syndrome, has been estimated to occur in 1% of the general adult population. Overlap patients have worse sleep-related hypoxaemia and hypercapnia than patients with COPD or OSA alone. OSA has a similar prevalence in COPD as in a general population of similar age, but oxygen desaturation during sleep is more pronounced when the two conditions coexist. Management of sleep-related problems in COPD should particularly focus on minimising sleep disturbance via measures to limit cough and dyspnoea; nocturnal oxygen therapy is not generally indicated for isolated nocturnal hypoxaemia. Treatment with continuous positive airway pressure alleviates hypoxaemia, reduces hospitalisation and pulmonary hypertension, and improves survival