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Semin Respir Crit Care Med 2025; 46(02): 95-97
DOI: 10.1055/a-2631-4757
Preface

When Sleep and Breathing Don't Play Well in the Sandbody…

Ferran Barbé
1   Translational Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova-Santa Maria, Lleida Institute for Biomedical Research Dr. Pifarré Foundation (IRBLleida), Lleida, Spain
2   CIBER of Respiratory diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
,
Adriano D. S. Targa
1   Translational Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova-Santa Maria, Lleida Institute for Biomedical Research Dr. Pifarré Foundation (IRBLleida), Lleida, Spain
2   CIBER of Respiratory diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
,
David Gozal
3   Department of Pediatrics and Office of the Dean, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia
› Author Affiliations
Funding None.
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Ferran Barbé, MD, FERS, ATSF
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Adriano D. S. Targa, PhD
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David Gozal, MD, MBA, PhD (Hon)

The International Classification of Sleep Disorders (ICSD), published by the American Academy of Sleep Medicine, serves as a standardized guide for the classification and definition of sleep disorders. The term sleep disorder encompasses any condition that disrupts normal sleep patterns, negatively affecting the quality, timing, or duration of sleep, and causing daytime distress or impairment in functioning. The most recent edition of the ICSD categorizes 143 distinct sleep disorders into seven primary groups: insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep–wake disorders, parasomnias, sleep-related movement disorders, and other sleep disorders.

This edition of Seminars in Respiratory and Critical Care Medicine includes comprehensive reviews by experts in the field, discussing critical aspects of several sleep disorders that are of relevance in the context of underlying respiratory disease. These chapters offer different perspectives on the topic: (1) Exploring how changes in sleep-related factors, such as duration and quality, are linked for example to outcomes of respiratory infections, lung cancer, and cardiovascular disease; (2) discussing the short-term and long-term impact of respiratory illnesses and their context on sleep and circadian rhythms; (3) examining specific sleep disorders, such as obstructive sleep apnea (OSA), and the implications imposed by the overlapping presence of OSA and respiratory conditions; and (4) addressing other aspects such as the role of nocturnal hypoxemia and pulmonary rehabilitation within this context.

Several studies have revealed connections between sleep disturbances and respiratory infections, a topic explored in depth in a chapter by Boira and collaborators.[1] The authors have highlighted how sleep disorders, especially OSA, may increase the susceptibility to respiratory infections. The characteristic perturbation elicited by the presence of OSA, namely intermittent hypoxia and fragmented sleep, generates and propagates a proinflammatory state, leading to sustained immune activation. This, in turn, contributes to immunosenescence, reduced ability to fend off microbial pathogen threats, thereby increasing the risk of bacterial and viral infections. Additional contributing factors include nocturnal microaspirations and comorbid conditions such as obesity and chronic obstructive pulmonary disease (COPD).

Lung cancer, the leading cause of cancer-related deaths globally, continues to rise in prevalence, emphasizing the need to identify risk factors that could modify disease occurrence and its progression. Growing recognition of the impact of sleep on oncogenesis and chemotherapeutic resistance is promising, as it may help identify unique therapeutic targets while also detecting populations at higher risk, thereby favoring prevention and overall outcomes among lung cancer patients. Cooper et al.[2] provide an insightful review on this topic, summarizing the evidence linking poor sleep quality, disrupted sleep duration, insomnia, OSA, evening chronotype, and peripheral limb movements during sleep to an increased risk of lung cancer development. These sleep-related factors also have potential implications for cancer survival outcomes. Proposed mechanisms for these associations include immune dysregulation, metabolic changes, and elevated levels of reactive oxygen species. The chapter also discusses how treatments aimed at improving sleep health may influence lung cancer outcomes.

Expanding on the connection between sleep disruptions and health outcomes, Pinilla and colleagues offer a thorough review of the current evidence on how various sleep dimensions, such as sleep duration, timing, quality, and regularity, affect cardiovascular health.[3] Their analysis also considers factors such as daytime napping, social jetlag, shift work, and chronotype. Additionally, the authors address how specific sleep disorders, including insomnia and sleep-disordered breathing, contribute to cardiovascular risk, while also considering multidimensional models of sleep health. Notwithstanding the extensive body of evidence, the authors conclude that while sleep is undeniably a cornerstone of overall health with significant implications for cardiovascular function, more research is needed. This research should integrate the multiple facets of sleep to fully understand the complex and possibly bidirectional relationships between sleep and cardiovascular health.

Sleep and circadian rhythm disturbances are frequently reported in specific settings, such as critical illnesses and COVID-19. The chapter by Pisani and colleagues offers a detailed review of sleep and circadian changes observed during intensive care unit (ICU) stays, and more importantly, after hospital discharge.[4] Similarly, Targa and colleagues explore these alterations following the acute phase of COVID-19, examining their manifestations, prevalence, and associated factors.[5] The authors also discuss how these disruptions may impact the risk of SARS-CoV-2 infection, the severity of COVID-19, and the development of post-COVID-19 conditions. Overall, the current evidence suggests that during ICU stays, patients typically experience poor sleep quality, as reported through questionnaires and complaints. Additionally, sleep parameters such as total sleep time, sleep efficiency, and the percentage of time spent in deeper sleep stages (slow wave sleep and REM sleep) are reduced, as indicated by polysomnography and actigraphy. Circadian rhythms are also disrupted, with alterations observed in the 24-hour patterns of melatonin, cortisol, blood pressure, heart rate, and body temperature, resulting in fragmented rhythms with reduced amplitude. After discharge from the ICU, some patients show slight improvements in sleep quality, while others do not, with similar variability observed in circadian rhythm recovery. Interestingly, improvements in sleep quality tend to correlate with better mental health outcomes, while circadian pattern recovery is often linked to factors such as ICU stay duration, the need for invasive mechanical ventilation, and respiratory function.

In the context of critical illness and COVID-19, pulmonary (and sleep) rehabilitation may prove essential in aiding recovery. Indeed, sleep plays a crucial role in processes like inflammation regulation and tissue repair, both of which are key to successful rehabilitation. Henríquez-Beltrán and colleagues offer a thorough review of the interactions between sleep, circadian rhythms, and respiratory function, emphasizing their relevance to pulmonary rehabilitation and recovery.[6]

OSA is a highly prevalent sleep disorder linked to increased risk of negative health outcomes. Continuous positive airway pressure (CPAP) remains the first-line treatment, especially for individuals with moderate to severe OSA. However, adherence to CPAP therapy is often suboptimal, prompting the need for alternative or adjunctive therapeutic strategies to better address patient symptoms and improve treatment outcomes. A deeper understanding of OSA endotypes and phenotypes offers a promising path toward more personalized care, allowing clinicians to tailor interventions based on the underlying mechanisms and individual patient profiles. In their chapter, Labarca and colleagues explore a range of therapeutic options, including both non-CPAP interventions and pharmacological treatments, within the framework of precision medicine.[7]

A sleep disorder that has recently re-emerged into attention (initially identified and described in 1973) is comorbid insomnia and sleep apnea (COMISA), a condition in which the two most common sleep disorders overlap. Despite its widespread occurrence, COMISA has often been overlooked, partly due to the conflicting symptoms between insomnia (such as hyperarousal and difficulty achieving and/or maintaining sleep) and OSA (including sleep fragmentation and excessive daytime sleepiness). Recent studies emphasize that COMISA is not simply the coexistence of insomnia and OSA but rather may involve distinct pathophysiological interactions and unique clinical phenotypes. COMISA has been linked to more significant impairments in sleep, daytime functioning, and both physical and mental health, compared with insomnia or OSA alone. Emerging research suggests that COMISA enhances the risk of cardiovascular and metabolic diseases and is associated with reduced adherence to positive airway pressure (PAP) therapy. The chapter by Meira e Cruz delves into the epidemiology, mechanisms, and clinical manifestations of this condition. It also discusses the key challenges in diagnosing COMISA while addressing available treatment options.

COPD and OSA frequently coexist, forming what is known as COPD/OSA overlap syndrome. This combination of conditions heightens the risk of COPD exacerbations and mortality. Patients with COPD/OSA overlap syndrome are also more likely to develop cardiometabolic diseases than those with either condition alone. Marin-Oto and colleagues offer an insightful review on the pathophysiology, clinical features, and management of COPD/OSA overlap syndrome, recommending CPAP for patients with severe OSA, which has been shown to alleviate daytime sleepiness, hypercapnia, and reduce COPD exacerbations.[8] For patients with persistent hypoxemia despite CPAP, supplemental oxygen may improve long-term outcomes.

García-Ortega and colleagues examined the intricate relationship between OSA and pulmonary embolism.[9] On one hand, the prevalence of OSA is notably higher in patients with acute pulmonary embolism. On the other hand, patients with OSA face an increased risk of developing acute pulmonary embolism, although a direct causal link has yet to be firmly established. Moreover, OSA plays a significant role in the prognosis of pulmonary embolism. Specifically, the presence of OSA alongside pulmonary embolism has been associated with worse short- and long-term outcomes. These findings highlight the importance of obtaining a thorough clinical sleep history for all patients presenting with acute pulmonary embolism. Furthermore, extensive research is needed to clearly define the bidirectional interactions between these two conditions, as they have important clinical implications for the management of both pulmonary embolism and OSA.

Obesity hypoventilation syndrome, characterized by the combination of obesity, sleep-disordered breathing, and daytime hypercapnia, is another disorder discussed in detail by Masa and colleagues.[10] The chapter explores the pathophysiological mechanisms underlying this syndrome, highlighting the importance of understanding its phenotype to better predict responses to various PAP therapies. Obesity hypoventilation syndrome presents as three primary phenotypes: hypoventilation without significant OSA, hypoventilation with significant OSA, and acute-on-chronic hypercapnic respiratory failure. CPAP and non-invasive ventilation (NIV) appear to offer comparable long-term effectiveness in patients with this severe OSA phenotype. For individuals without significant OSA, NIV is generally the preferred treatment approach as well and is also likely the most suitable option for those presenting with the acute-on-chronic hypercapnic respiratory failure phenotype.

The coexistence of three interrelated conditions, asthma, obesity, and OSA, represents a complex clinical scenario that warrants closer examination. These disorders frequently share overlapping pathophysiological mechanisms and symptoms, and when they occur together, each can intensify the severity of the other. For instance, individuals with asthma and obesity often experience poorer asthma control, heightened disease severity, and more frequent exacerbations. Obesity itself is a well-established risk factor for OSA, while OSA can, in turn, aggravate asthma symptoms through mechanisms such as intermittent hypoxia and sleep fragmentation, increased inflammation both systemic and in the lung, leading to heightened instability of the disease and making clinical management more challenging. In their chapter, Rodriguez and Sharma explore the intricate interactions among these three conditions, emphasizing the need for integrated and comprehensive treatment strategies.

Nocturnal hypoxemia is a common and clinically significant feature across various respiratory disorders, with considerable implications for patient outcomes and treatment planning. Oximetry, a non-invasive and widely used diagnostic tool, facilitates the evaluation of nocturnal oxygenation by measuring a range of oxyhemoglobin saturation (SpO2)-based indicators. Although these measurements are well-validated in the context of OSA, their relevance and application in other respiratory conditions, such as COPD, pulmonary hypertension, obesity hypoventilation syndrome, heart failure, neuromuscular diseases, pregnancy, and in individuals residing at high altitudes are still being explored. In their chapter, Hajipour and colleagues examine the pathophysiological basis of hypoxemia across these different clinical scenarios and assess how SpO2-derived metrics can contribute to risk stratification beyond OSA.[11] They also highlight the interpretative challenges associated with oximetry and discuss its technical limitations.

We hope that these issues with such expansive and comprehensive content will be both informative and useful to your research or clinical practice, and that it will foster novel avenues for improving the outcomes of many respiratory diseases by enhancing our understanding of the contributions of underlying sleep perturbations.



Publication History

Article published online:
01 August 2025

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