Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in which the airways narrow or collapse during sleep, causing obstructive apnea. The prevalence of OSAS continues to rise worldwide, particularly middle-aged and elderly individuals. mechanism upper airway incompletely understood but associated with several factors, including obesity, craniofacial changes, altered muscle function airway, pharyngeal neuropathy, fluid shifts neck. main characteristics are recurrent pauses respiration, lead intermittent hypoxia (IH) hypercapnia, accompanied by blood oxygen desaturation arousal sharply increases risk diseases. This paper first briefly describes epidemiology, incidence, pathophysiological mechanisms OSAS. Next, alterations relevant signaling pathways induced IH systematically reviewed discussed. For example, can induce gut microbiota (GM) dysbiosis, impair intestinal barrier, alter metabolites. These ultimately secondary oxidative stress, systemic inflammation, sympathetic activation. We then summarize effects on disease pathogenesis, cardiocerebrovascular disorders, neurological metabolic diseases, cancer, reproductive COVID-19. Finally, different therapeutic strategies for caused causes proposed. Multidisciplinary approaches shared decision-making necessary successful treatment future, more randomized controlled trials needed further evaluation define what treatments best specific patients.

Language: Английский

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A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2022, Volume and Issue: 205(12), P. 1461 - 1469

Published: Feb. 25, 2022

Rationale: Current therapies for obstructive sleep apnea (OSA) are limited by insufficient efficacy, compliance, or tolerability. An effective pharmacological treatment OSA is warranted. Carbonic anhydrase inhibition has been shown to ameliorate OSA. Objectives: To explore safety and tolerability of the carbonic inhibitor sulthiame (STM) in Methods: A 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted patients with moderate and/or severe not tolerating positive airway pressure treatment. Measurements Main Results: Intermittent paresthesia reported 79%, 67%, 18% receiving 400 mg STM (n = 34), 200 12), placebo 22), respectively. Dyspnea after (18%). Six higher dose group withdrew because adverse events. There were no serious reduced apnea–hypopnea index from 55.2 33.0 events/h (−41.0%) 400-mg 61.1 40.6 (−32.1%) (P < 0.001 both). Corresponding values 53.9 50.9 (−5.4%). The reduction threshold ⩾50% reached 40% mg, 25% 5% placebo. Mean overnight oxygen saturation improved 1.1% P 0.034, respectively). Patient-related outcomes unchanged. Conclusions: showed a satisfactory profile OSA, on average, more than 20 events/h, one strongest reductions drug Larger scale clinical studies justified. Clinical registered www.clinicaltrialsregister.eu (2017-004767-13).

Language: Английский

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Current and novel treatment options for obstructive sleep apnoea

ERJ Open Research, Journal Year: 2022, Volume and Issue: 8(2), P. 00126 - 2022

Published: April 1, 2022

Obstructive sleep apnoea is a challenging medical problem due to its prevalence, impact on quality of life and performance in school professionally, the implications for risk accidents, comorbidities mortality. Current research has carved out broad spectrum clinical phenotypes defined major pathophysiological components. These findings point concept personalised therapy, oriented both distinct presentation most relevant pathophysiology individual patient. This leads questions whether sufficient therapeutic options other than positive airway pressure (PAP) alone are available, which patients they may be useful, if there specific indications single or combined treatment, solid scientific evidence recommendations. review describes our knowledge PAP non-PAP therapies address upper collapsibility, muscle responsiveness, arousability respiratory drive. The heterogeneous, including technical pharmaceutical already use at an advanced experimental stage. Although obvious need more therapies, available data demonstrate variety effective options, should replace unidirectional focus therapy.

Language: Английский

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Central sleep apnoea: not just one phenotype

European Respiratory Review, Journal Year: 2024, Volume and Issue: 33(171), P. 230141 - 230141

Published: Jan. 31, 2024

Recent scientific findings in the field of sleep disordered breathing have characterised a variety phenotypes obstructive apnoea. These prompted investigations aiming to achieve more precise differentiation and description entities central apnoea (CSA). There is increasing evidence for heterogeneity CSA terms underlying aetiology, pathophysiological concepts, treatment response outcome. Assigning patients these allows selection individualised therapies. Major characteristics include loop gain, apnoeic threshold, regulation neuromuscular mechanics. Chronic heart failure most important disease, leading nonhypercapnic based on increased controller gain. Although many questions remain, this review tries describe current knowledge pathophysiology clinical entities. The prognostic aspects may guide indication pharmacotherapy invasive options. In addition, paper provides an update understanding adaptive servo-ventilation its role CSA.

Language: Английский

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Treatment of OSA and its Impact on Cardiovascular Disease, Part 2

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 84(13), P. 1224 - 1240

Published: Sept. 1, 2024

Language: Английский

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Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea

Sleep Medicine, Journal Year: 2023, Volume and Issue: 107, P. 137 - 148

Published: April 19, 2023

Language: Английский

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Sex-specific age-related worsening of pathological endotypic traits in patients with obstructive sleep apnea

SLEEP, Journal Year: 2024, Volume and Issue: 48(1)

Published: Aug. 11, 2024

Abstract Study Objectives Obstructive sleep apnea (OSA) is more prevalent in men and older adults. Few studies have explored variations pathological endotypic traits by age sex using a large patient sample, offering insights into the development of disease. Our study aims to examine how endotype characteristics OSA vary across ages different sex. Methods A cross-sectional was conducted, enrolling 2296 adult patients referred for in-laboratory diagnostic polysomnography at single center Taiwan. Among them, 1374 had an apnea–hypopnea index ≥5. Using “Phenotyping Polysomnography” method, we estimated four traits—arousal threshold, upper airway collapsibility, loop gain, muscle compensation. Demographic polysomnographic were compared between sexes groups. Generalized linear regression generalized additive models employed explore associations with traits. Results Men exhibited higher collapsibility lower compensation than women (difference: 4.32 %eupnea 4.49 %eupnea, respectively). Younger prevalence obesity, snoring symptoms, gain patients. For men, correlated increased decreased arousal threshold after 37 years old. Whereas women, not associated age, except increase advancing age. Conclusions Personalized treatment options should take consideration Reducing could be objective OSA.

Language: Английский

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JCS 2023 Guideline on Diagnosis and Treatment of Sleep Disordered Breathing in Cardiovascular Disease

Circulation Journal, Journal Year: 2024, Volume and Issue: 88(11), P. 1865 - 1935

Published: Aug. 25, 2024

Language: Английский

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Continuous positive airway pressure and adherence in patients with different endotypes of obstructive sleep apnea

Journal of Sleep Research, Journal Year: 2023, Volume and Issue: 33(1)

Published: July 15, 2023

Summary Determining the endotypes of obstructive sleep apnea (OSA) has potential implications for precision interventions. Here we assessed whether continuous positive airway pressure (CPAP) treatment outcomes differ across endotypic subgroups. We conducted a retrospective analysis data obtained from 225 patients with moderate‐to‐severe OSA single centre. Polysomnographic and CPAP titration study were collected between May 2020 January 2022. One‐month adherence was followed. Obstructive endotypes, namely arousal threshold, collapsibility, loop gain, upper gain estimated polysomnography dichotomised as high versus low. examined associations subgroups (1) optimal pressure, (2) CPAP‐related improvements in architecture (proportions slow‐wave rapid eye movement (REM) sleep), (3) adherence. observed that collapsibility required higher than those low (∆ = 0.4 cmH 2 O, 95% confidence interval [CI] 0.3–1.7). A larger increase REM proportions after or levels endotypes. High independently associated longer use hours per night 0.6 h, CI 0.2–1.5 ∆ 0.3 0.03–1.5, respectively). In conclusion, different exhibit difference treatment. Knowledge may help clinicians to understand which are expected benefit most therapy prior its administration.

Language: Английский

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Effects of Sacubitril-Valsartan on Clinical, Echocardiographic, and Polygraphic Parameters in Patients Affected by Heart Failure With Reduced Ejection Fraction and Sleep Apnea

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: April 5, 2022

Heart failure with reduced ejection fraction (HFrEF) is a clinical condition frequently diagnosed in practice. In patients affected by HFrEF, sleep apnea (SA) can be detected among the most frequent comorbidities. Sacubitril-valsartan (sac/val) association has been proven to effective reducing disease progression and all-cause mortality HFrEF patients. Sac/val treatment potentially attenuate SA development via several pathophysiologic mechanisms, including improvement of global hemodynamics, reduction extracellular fluid overload, decrease sympathetic neural activity.We recruited 132 SA, already under continuous positive airway pressure (CPAP), which was discontinued 24 h before scheduled study timepoints. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, laboratory tests were performed each patient at baseline after 6-month sac/val.After 6 months, sac/val induced statistically significant changes clinical, hemodynamic, biohumoral (NT-proBNP, serum electrolytes, creatinine, uric acid), echocardiographic parameters. particular, cardiac index (CI), both atrial ventricular volumes longitudinal strain (GLS) improved. Moreover, polysomnography, carried out during temporary CPAP interruption, revealed apnea-hypopnea (AHI) value (p < 0.0001), central AHI obstructive oxygen desaturation (ODI) percentage time saturation below 90% (TC90) 0.0001). The CI, estimated glomerular filtration rate (eGFR), NT-proBNP, tricuspid annular plane excursion (TAPSE) contributed 23.6, 7.6, 7.3, 4.8% variability, respectively, whole model accounted for 43.3% variation.Our results suggest that able significantly improve cardiorespiratory performance integrating impact CPAP. Thus, therapy may synergistically contribute lower risks pulmonary complications SA.

Language: Английский

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