Interesting articles

@article{Dirk2020,
title = {On the rise and fall of the apnea-hypopnea index: A historical review and critical appraisal},
author = {Dirk, A Pevernagie and Barbara, Gnidovec, Strazisar and Ludger, Grote and Raphael, Heinzer and Walter, T McNicholas and Thomas, Penzel and Winfried, Randerath and Sophia, Schiza and Johan, Verbraecken and Erna, Sif Arnardottir},
url = {https://pubmed.ncbi.nlm.nih.gov/32406974/},
year = {2020},
date = {2020-05-14},
abstract = {The publication of "The Sleep Apnea Syndromes" by Guilleminault et al. in the 1970s hallmarked the discovery of a new disease entity involving serious health consequences. Obstructive sleep apnea was shown to be the most important disorder among the sleep apnea syndromes (SAS). In the course of time, it was found that the prevalence of obstructive sleep apnea reached the proportions of a global epidemic, with a major impact on public health, safety and the economy. Early on, a metric was introduced to gauge the seriousness of obstructive sleep apnea, based on the objective measurement of respiratory events during nocturnal sleep. The apnea index and later on the apnea-hypopnea index, being the total count of overnight respiratory events divided by the total sleep time in hours, were embraced as principle measures to establish the diagnosis of obstructive sleep apnea and to rate its severity. The current review summarises the historical evolution of the apnea-hypopnea index, which has been subject to many changes, and has been criticised for not capturing relevant clinical features of obstructive sleep apnea. In fact, the application of the apnea-hypopnea index as a continuous exposure variable is based on assumptions that it represents a disease state of obstructive sleep apnea and that evocative clinical manifestations are invariably caused by obstructive sleep apnea if the apnea-hypopnea index is above diagnostic threshold. A critical appraisal of the extensive literature shows that both assumptions are invalid. This conclusion prompts a reconsideration of the role of the apnea-hypopnea index as the prime diagnostic metric of clinically relevant obstructive sleep apnea.},
keywords = {Diagnosis, Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Unnur2018,
title = {Obesity modulates the association between sleep apnea treatment and CHI3L1 levels but not CHIT1 activity in moderate to severe OSA: an observational study},
author = {Unnur, Diljá Teitsdóttir and Erna, Sif Arnardóttir and Erla, Björnsdóttir and Þórarinn, Gíslason and Pétur, Henry Petersen},
url = {https://pubmed.ncbi.nlm.nih.gov/30311184/},
year = {2018},
date = {2018-10-11},
abstract = {Purpose: The inflammatory markers chitinase-3-like protein 1 (CHI3L1) and chitotriosidase (CHIT1) have both been associated with cardiovascular complications. The aim of this preliminary observational study was to assess the roles and interaction of obstructive sleep apnea (OSA) severity and body mass index (BMI) with plasma CHI3L1 levels and CHIT1 activity in patients with moderate to severe OSA. The second aim was to assess the roles and interaction of positive airway pressure (PAP) treatment and BMI on the expression of the same proteins.

Methods: The study included 97 OSA patients with an apnea-hypopnea index (AHI) ≥ 15 and full usage of PAP treatment after 4 months. Plasma CHI3L1 levels and CHIT1 activity were measured before and after treatment.

Results: Multiple linear regression analysis demonstrated an independent association of BMI on CHI3L1 levels (p < 0.05) but not on CHIT1 activity. The OSA severity markers (AHI and oxygen desaturation index) did not independently or in interaction with BMI levels associate with CHI3L1 levels or with CHIT1 activity (p > 0.05). A two-way repeated measures ANOVA revealed a significant interaction between PAP treatment effect (before vs. after) and BMI groups (< 35 kg/m2 vs. ≥ 35 kg/m2) on CHI3L1 levels (p = 0.03) but not on CHIT1 activity (p = 0.98).

Conclusions: Obesity independently associated with CHI3L1 levels. Association between OSA severity and CHI3L1 levels or CHIT1 activity (independent of or dependent on obesity level) could not be confirmed. However, decrease was observed in CHI3L1 levels after PAP treatment in severely obese OSA patients but not in those less obese.},
keywords = {Positive airway pressure, Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Brendan2018,
title = {Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis},
author = {Brendan, T Keenan and Jinyoung, Kim and Bhajan, Singh and Lia, Bittencourt and Ning-Hung, Chen and Peter, A Cistulli and Ulysses, J Magalang and Nigel, McArdle and Jesse, W Mindel and Bryndís, Benediktsdóttir and Erna, Sif Arnardóttir and Lisa, Kristin Prochnow and Thomas, Penzel and Bernd, Sanner and Richard, J Schwab and Chol, Shin and Kate, Sutherland and Sergio, Tufik and Greg, Maislin and Þórarinn, Gíslason and Allan, I Pack},
url = {https://academic.oup.com/sleep/article/41/3/zsx214/4791307},
year = {2018},
date = {2018-01-05},
abstract = {Study Objectives
A recent study of patients with moderate–severe obstructive sleep apnea (OSA) in Iceland identified three clinical clusters based on symptoms and comorbidities. We sought to verify this finding in a new cohort in Iceland and examine the generalizability of OSA clusters in an international ethnically diverse cohort.

Methods
Using data on 972 patients with moderate–severe OSA (apnea–hypopnea index [AHI] ≥ 15 events per hour) recruited from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), we performed a latent class analysis of 18 self-reported symptom variables, hypertension, cardiovascular disease, and diabetes.

Results
The original OSA clusters of disturbed sleep, minimally symptomatic, and excessively sleepy replicated among 215 SAGIC patients from Iceland. These clusters also generalized to 757 patients from five other countries. The three clusters had similar average AHI values in both Iceland and the international samples, suggesting clusters are not driven by OSA severity; differences in age, gender, and body mass index were also generally small. Within the international sample, the three original clusters were expanded to five optimal clusters: three were similar to those in Iceland (labeled disturbed sleep, minimal symptoms, and upper airway symptoms with sleepiness) and two were new, less symptomatic clusters (labeled upper airway symptoms dominant and sleepiness dominant). The five clusters showed differences in demographics and AHI, although all were middle-aged (44.6–54.5 years), obese (30.6–35.9 kg/m2), and had severe OSA (42.0–51.4 events per hour) on average.

Conclusions
Results confirm and extend previously identified clinical clusters in OSA. These clusters provide an opportunity for a more personalized approach to the management of OSA.},
keywords = {Daytime sleepiness, Insomnia, Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Erna2016,
title = {Obstructive sleep apnoea in the general population: highly prevalent but minimal symptoms},
author = {Erna, Sif Arnardóttir and Erla, Björnsdóttir and Kristín, A Ólafsdóttir and Bryndís, Benediktsdóttir and Þórarinn, Gíslason},
url = {https://erj.ersjournals.com/content/47/1/194.short},
year = {2016},
date = {2016-01-01},
abstract = {The aim was to assess the prevalence of obstructive sleep apnoea (OSA) as defined by an apnoea–hypopnea index (AHI) ≥15 in the middle-aged general population, and the interrelationship between OSA, sleep-related symptoms, sleepiness and vigilance.

A general population sample of 40–65-year-old Icelanders was invited to participate in a study protocol that included a type 3 sleep study, questionnaire and a psychomotor vigilance test (PVT).

Among the 415 subjects included in the study, 56.9% had no OSA (AHI <5), 24.1% had mild OSA (AHI 5–14.9), 12.5% had moderate OSA (AHI 15–29.9), 2.9% had severe OSA (AHI ≥30) and 3.6% were already diagnosed and receiving OSA treatment. However, no significant relationship was found between AHI and subjective sleepiness or clinical symptoms. A relationship with objective vigilance assessed by PVT was only found for those with AHI ≥30. Subjects already on OSA treatment and those accepting OSA treatment after participating in the study were more symptomatic and sleepier than others with similar OSA severity, as assessed by the AHI.

In a middle-aged general population, approximately one in five subjects had moderate-to-severe OSA, but the majority of them were neither symptomatic nor sleepy and did not have impaired vigilance.},
keywords = {Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Lichuan2014,
title = {The different clinical faces of obstructive sleep apnoea: a cluster analysis},
author = {Lichuan, Ye and Grace, W Pien and Sarah, J Ratcliffe and Erla, Björnsdóttir and Erna, Sif Arnardóttir and Allan, I Pack and Bryndís, Benediktsdóttir and Þórarinn, Gíslason},
url = {https://erj.ersjournals.com/content/44/6/1600.short},
year = {2014},
date = {2014-11-30},
abstract = {Although commonly observed in clinical practice, the heterogeneity of obstructive sleep apnoea (OSA) clinical presentation has not been formally characterised.

This study was the first to apply cluster analysis to identify subtypes of patients with OSA who experience distinct combinations of symptoms and comorbidities. An analysis of baseline data from the Icelandic Sleep Apnoea Cohort (822 patients with newly diagnosed moderate-to-severe OSA) was performed.

Three distinct clusters were identified. They were classified as the “disturbed sleep group” (cluster 1), “minimally symptomatic group” (cluster 2) and “excessive daytime sleepiness group” (cluster 3), consisting of 32.7%, 24.7% and 42.6% of the entire cohort, respectively. The probabilities of having comorbid hypertension and cardiovascular disease were highest in cluster 2 but lowest in cluster 3. The clusters did not differ significantly in terms of sex, body mass index or apnoea–hypopnoea index.

Patients with OSA have different patterns of clinical presentation, which need to be communicated to both the lay public and the professional community with the goal of facilitating care-seeking and early identification of OSA. Identifying distinct clinical profiles of OSA creates a foundation for offering more personalised therapies in the future.},
keywords = {Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Erla2013,
title = {Symptoms of Insomnia among Patients with Obstructive Sleep Apnea Before and After Two Years of Positive Airway Pressure Treatment.},
author = {Erla, Björnsdóttir and Christer, Janson and Jón, F Sigurðsson and Philip, Gehrman and Michael, Perlis and Sigurður, Júlíusson and Erna, Sif Arnardóttir and Samuel, T Kuna and Allan, I Pack and Þórarinn, Gíslason and Bryndís, Benediktsdóttir},
url = {https://academic.oup.com/sleep/article/36/12/1901/2709415},
year = {2013},
date = {2013-12-01},
abstract = {Study Objectives:
To assess the changes of insomnia symptoms among patients with obstructive sleep apnea (OSA) from starting treatment with positive airway pressure (PAP) to a 2-y follow-up.

Design:
Longitudinal cohort study.

Setting:
Landspitali—The National University Hospital of Iceland.

Participants:
There were 705 adults with OSA who were assessed prior to and 2 y after starting PAP treatment.

Intervention:
PAP treatment for OSA.

Measurements and Results:
All patients underwent a medical examination along with a type 3 sleep study and answered questionnaires on health and sleep before and 2 y after starting PAP treatment. The change in prevalence of insomnia symptoms by subtype was assessed by questionnaire and compared between individuals who were using or not using PAP at follow-up. Symptoms of middle insomnia were most common at baseline and improved signifcantly among patients using PAP (from 59.4% to 30.7%, P < 0.001). Symptoms of initial insomnia tended to persist regardless of PAP treatment, and symptoms of late insomnia were more likely to improve among patients not using PAP. Patients with symptoms of initial and late insomnia at baseline were less likely to adhere to PAP (odds ratio [OR] 0.56, P = 0.007, and OR 0.53, P < 0.001, respectively).

Conclusion:
Positive airway pressure treatment significantly reduced symptoms of middle insomnia. Symptoms of initial and late insomnia, however, tended to persist regardless of positive airway pressure treatment and had a negative effect on adherence. Targeted treatment for insomnia may be beneficial for patients with obstructive sleep apnea comorbid with insomnia and has the potential to positively affect adherence to positive airway pressure.},
keywords = {Insomnia, Positive airway pressure, Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Erna2012,
title = {The Interaction of Obstructive Sleep Apnea and Obesity on the Inflammatory Markers C-Reactive Protein and Interleukin-6: The Icelandic Sleep Apnea Cohort},
author = {Erna, Sif Arnardóttir and Greg, Maislin and Richard, J Schwab and Bethany, Staley and Bryndís, Benediktsdóttir and Ísleifur, Ólafsson and Sigurður, Júlíusson and Micah, Romer and Þórarinn, Gíslason and Allan, I Pack},
url = {https://academic.oup.com/sleep/article/35/7/921/2558872},
year = {2012},
date = {2012-07-01},
abstract = {Study Objectives:
To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels.

Design:
Cross-sectional cohort.

Setting:
The Icelandic Sleep Apnea Cohort.

Participants:
454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr.

Interventions:
N/A.

Measurements and Results:
Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO2) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m2). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO2 only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women.

Conclusions:
OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients.},
keywords = {Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Erla2011,
title = {Insomnia in untreated sleep apnea patients compared to controls.},
author = {Erla, Björnsdóttir and Christer, Janson and Þórarinn, Gíslason and Jón, F Sigurðsson and Allan, I Pack and Philip, Gehrman and Bryndís, Benediktsdóttir},
url = {https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2869.2011.00972.x},
year = {2011},
date = {2011-10-12},
abstract = {Insomnia and obstructive sleep apnea (OSA) often coexist, but the nature of their relationship is unclear. The aims of this study were to compare the prevalence of initial and middle insomnia between OSA patients and controls from the general population as well as to study the influence of insomnia on sleepiness and quality of life in OSA patients. Two groups were compared, untreated OSA patients (n = 824) and controls ≥ 40 years from the general population in Iceland (n = 762). All subjects answered the same questionnaires on health and sleep and OSA patients underwent a sleep study. Altogether, 53% of controls were males compared to 81% of OSA patients. Difficulties maintaining sleep (DMS) were more common among men and women with OSA compared to the general population (52 versus 31% and 62 versus 31%, respectively, P < 0.0001). Difficulties initiating sleep (DIS) and DIS + DMS were more common among women with OSA compared to women without OSA. OSA patients with DMS were sleepier than patients without DMS (Epworth Sleepiness Scale: 12.2 versus 10.9, P < 0.001), while both DMS and DIS were related to lower quality of life in OSA patients as measured by the Short Form 12 (physical score 39 versus 42 and mental score 36 versus 41, P < 0.001). DIS and DMS were not related to OSA severity. Insomnia is common among OSA patients and has a negative influence on quality of life and sleepiness in this patient group. It is relevant to screen for insomnia among OSA patients and treat both conditions when they co‐occur.},
keywords = {Insomnia, Risk factors, Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}

@article{Erna2009,
title = {Molecular signatures of obstructive sleep apnea in adults: a review and perspective},
author = {Erna, Sif Arnardóttir and Miroslaw, Mackiewicz and Þórarinn, Gíslason and Karen, L Teff and Allan, I Pack},
url = {https://academic.oup.com/sleep/article/32/4/447/3741709},
year = {2009},
date = {2009-08-01},
abstract = {The consequences of obstructive sleep apnea (OSA) are largely mediated by chronic intermittent hypoxia and sleep fragmentation. The primary molecular domains affected are sympathetic activity, oxidative stress and inflammation. Other affected domains include adipokines, adhesion molecules and molecules that respond to endoplasmic reticulum stress. Changes in molecular domains affected by OSA, assessed in blood and/or urine, can provide a molecular signature for OSA that could potentially be used diagnostically and to predict who is likely to develop different OSA-related comorbidities. High-throughput discovery strategies such as microarrays, assessing changes in gene expression in circulating blood cells, have the potential to find new candidates and pathways thereby expanding the molecular signatures for OSA. More research is needed to fully understand the pathophysiological significance of these molecular signatures and their relationship with OSA comorbidities. Many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA. Moreover, obesity affects the same molecular pathways as OSA. Thus, a challenge to establishing a molecular signature for OSA is to separate the effects of OSA from obesity. We propose that the optimal strategy is to evaluate the temporal changes in relevant molecular pathways during sleep and, in particular, the alterations from before to after sleep when assessed in blood and/or urine. Such changes will be at least partly a consequence of chronic intermittent hypoxia and sleep fragmentation that occurs during sleep.},
keywords = {Pathophysiology, Sleep Apnea},
pubstate = {published},
tppubtype = {article}
}